What we know and don't know about the development of independent ingestion in rats

Appetite, 1985, 6, 333-356

What We Know and Don't Know About the Development of Independent Ingestion in Rats W. G. HALL Department of Psychology, Duke University

Because suckling behavior differs in many ways from later ingestive behavior, the development of feeding and drinking in rats is best studied apart from the normal suckling situation. Newborn rat pups, separated from their mothers, will actively ingest diet infused into their mouths or spread on the floor beneath them. Such "independent" ingestion resembles the ingestive behavior of adult animals, but it also undergoes developmental changes in organization and control during the preand post-weaning periods: (a) When young, deprived pups are fed, they show generalized, non-directed behavioral excitement; but with increasing age, this generalized responding matures into directed and focused ingestive activity. (b) Early independent ingestion depends on a warm test environment; but with development, other familiar environmental and social cues come to influence responding. (c) The internal controls of ingestion also change. Only gastric distension and hydrational status seem to be involved in controlling intake volume during early ingestion, with other ingestive controls emerging later in development. Thus ingestion, independent of suckling from the mother, is a system undergoing revealing developmental changes. These changes offer opportunities for studying ingestion, its controls, and its neural basis at its simplest organizational stage in the newborn, and at higher levels of complexity as maturation adds new components to the feeding system.

1. THE ORIGINS OF INGESTIVE BEHAVIOR Suckling is a mammal's first form of ingestion and thus it would seem to be a natural starting point for analysis of the development of feeding. However, after studying the suckling behavior of infant rats for a number of years, I, my collaborators, and many others studying feeding development have come to the conclusion that suckling, at least for the first week or two of a rat's life, has only limited similarity to adult ingestive behaviors (Blass & Cramer, 1982; Drewett, 1978; Epstein, in press; Hall, 1979; Hall & Williams, 1983). Thus, suckling probably does not represent an appropriate starting point for developmental analysis of adult forms of ingestive behavior. Several types of evidence caused us to question the continuity or homology between early suckling and adult modes of ingestion in rats (reviewed in Hall & Williams, 1983). Briefly, suckling differs from later ingestion in: the motor pattern

This review is part of a symposium on the ontogeny of ingestive behavior, guest-edited by Bennett G. Galef, Jr. Many of the studies described in this review were supported by a grant from the National Institute for Child Health and Human Development (HD 17457). I am grateful to B. G. Galef, Jf. for encouragement and suggestions and to S. Coyle, C. B. Phifer and 1. Terry for critical comments on earlier versions of the manuscript. Reprint requests should be addressed to W. G. Hall, Department of Psychology, Duke University, Durham, NC 27706, U.S.A. 0195-6663,85/04033 + 24 $03·000

D 1985 Academic Press Inc.,(London) Limited

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involved in consumatory responding; external controls; internal controls; experiential determinants; and neural substrate. Even in the absence of these differences, the intermittent availability of milk during normal suckling means that the regulatory processes that influence suckling intake during nursing cannot be directly compared to those in typical feeding studies with adult rodents; where an animal's appetitive behavior (i.e. initiating or terminating ingestion), rather than the vigor of its ingestive responses during a short period of food availability, influences volume consumed. These arguments do not deny that there are factors that modulate intake during suckling (e.g. Brake, Wolfson & Hofer, 1979; Brake, Sager, Sullivan & Hofer, 1982), or that there may be some overlap between suckling and later forms of ingestion, particularly with respect to suckling after the first two weeks of life. They do caution that suckling necessarily involves numerous mother-infant transactions besides those providing infants food (e.g. transferring warmth, establishing social relationships, etc.) as well as a form of nutrient availability that is very different from that for later ingestion. These considerations suggest that we view suckling as a highly specialized form of feeding, an 'ontogenetic adaptation' in Oppenheim's (1981) terms. For good reasons (e.g. maximizing intake and growth), suckling, especially early suckling, may be a very different process, or behavioral system, from ingestion 'independent' of the mother. If suckling isn't an appropriate precursor for the analysis of feeding and drinking, what then? One could await the normal post-weaning emergence of ingestive patterns typical of adults (Figure 1). But this might be too late in development to witness important events in ingestive ontogeny. Instead, we have sought an early precursor to adult ingestion which is different from suckling. I believe that such a system has been found in infant rats, one that is independent of suckling and that shares many characteristics with adult ingestive behavior (Hall, 1979; Wirth & Epstein, 1976). I will review here work from my laboratory and others based on this non-suckling system of independent ingestive behavior in infant rats. The work discussed provides a starting point for further investigation of ingestive ontogeny, and highlights some basic developmental events in ingestive organization and control. The recent research also provides an introduction to several conceptual issues. More importantly, its incompleteness points out areas of our ignorance about ingestive development.

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Timing of some of the major events in the development of rats.

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METHODS FOR STUDYING THE EARLY INDEPENDENT INGESTION OF RATS

I begin with a description of techniques for studying independent ingestion that we and others have been using with developing rats (a thorough description of these and other procedures for use in developing rats can be found in Phifer & Hall, in press). Imbedded in these methods is a conceptualization of ingestion as a dynamically shifting complex of component systems (Ziegler, 1976), a subset of these components being obvious in the sequence of behaviors for ingestion (e.g. increased activity, food search, identification, and the initiation, maintenance and termination of ingestion; also see Smith & Gibbs, 1979). Thus, any given ingestive test is designed to assess animals' competence with respect to particular components in this sequence (Table 1).

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FIGURE 2. (a). Diagram of sagittal sections through a young rat pup's head showing the location of posterior and anterior oral cannulas. (b). Drawing of a 6-day-old rat pup with cannula installed. The pup is probing the floor as an oral infusion is made.

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TABLE

1

Tests of independent ingestion for developing rats Procedure

Behavioral component sampled

Oral infusion; posterior cannula Oral infusion; anterior cannula' Diet spread on surface Diet in localized area Operant delivery of food

Reflex swallowing Movement of diet to back of mouth b Extension of ingestion into environment b Directing ingestion to restricted sources b Incorporating learned responses into feeding

'Additional fractionation of components of behavior may also be obtained by comparing pulsed infusions with continuous infusions. b Short tests (e.g. 10 min) using each of these procedures sample initial willingness to ingest. while longer tests (c.g. 30 min) sample the termination phase of ingestion.

The Mouth

In an elaboration of a technique first described by Wirth & Epstein (1976), we have simply delivered diet into the mouths of young rat pups to ask if they were willing to ingest the solution. A fine cannula implanted in the pup's mouth was used to provide programmed diet infusions (Figure 2, Hall, 1979). These cannulas can be placed in the mouth in a number of positions so that infused solutions will emerge in different locations (Kehoe & Blass, 1985; Hall, 1979). For the purposes of this discussion, infusions made through cannulas implanted in the back of the mouth stimulate swallowing that appears reflexive (though see Hall, 1979), whereas cannulas implanted in the front of the mouth allow infusions to spill out unless pups actively lick, lap, and swallow. Diet is infused at rates faster than pups typically swallow, to avoid absolute ceilings on intake, and intake is determined by weight gain. Ingestive tests using these procedures and the ones that follow can be brief(e.g. 10 min), so as to assess pups' initial willingness to ingest, or they can be of extended duration (e.g. 30 min) to study processes involved in the termination of ingestion. Feeding from External Sources

What a pup does with diet that is infused into its mouth provides information about the last stages in the ingestive response sequence. As one moves earlier in the sequence, further from the pup's mouth, greater ingestive competence is required. As a first step in testing pups' ability and willingness to approach and consume food from the environment, diet can be made available (in soaked toweling) on the floor of pups' test containers. To feed in this setting, pups must recognize food in their environment and put their mouths to the floor to initiate ingestion. Food Orientation

An additional component of ingestion, the ability to locate, orient to, and maintain contact with a diet source can be evaluated by restricting diet to a localized region on the floor of the test container. The effectiveness of ingestion from this restricted source can be compared to ingestion from a larger substrate to provide an indication of pup's ability to guide and direct their ingestive responding. We have also been able to study the ability of pups to use learned operant responses to feed in a miniaturized operant setting (Figure 3; Johanson & Hall, 1979).

337

INGESTIVE DEVELOPMENT Outside incubator

Inside incubator

FIGURE 3. Operant situation for newborn rat pups. The chamber is a styrofoam coffee cup, cut away here to show a pup inside with an oral cannula. Upward probing into a paddle (or one of the two paddles in the discrimination situation shown here) produces a small oral infusion of milk as a reward (from Johanson & Hall, 1979).

Behavioral Observations

With each of these procedures, in addition to measuring intake, pups' ingestive behavior and general activity can be observed and quantified at various points in time. We have tested pups in clear plastic test containers placed in transparent observation incubators and used several behavioral rating protocols (Hall, 1979). In summary, a range of ingestive test procedures and detailed behavioral analyses are available for studying feeding development. We and others have used these procedures to begin to describe pups' emerging independent ingestive competence and controls in terms of specific components in the ingestive sequence.

3.

EARLY INGESTION: WHAT'S PRESENT IN NEONATES (TO ABOUT

6

DAYS OF AGE)?

a. Behavioral Organization An ingestive response system From the time they are born, infant rats will make ingestive responses to oral infusions of milk (Hall, 1979; Wirth & Epstein, 1976). In fact, we recently have observed such ingestive responding in infants delivered prematurely by caesarian section (Terry & Hall, Note 1). When young, deprived pups receive infusions of diet (usually, commercially available 'Half & Half), they respond with active licking, lapping, and swallowing and they make mouthing movements with their jaws that resemble adult

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ingestive responses. This adult-like consummatory response is visibly different from the unique consummatory 'stretch' response for milk intake that characterizes suckling, and which is unlike later feeding. Thus, an adult-like ingestive system is already developed in newborn rats, and anticipates later function (Anokhin, 1964). An affective response Deprived pups (deprivation produced by removing pups from their mother and placing them in a warm humidified incubator), 6 days of age and younger, also show a dramatic behavioral excitement when fed with oral infusions (Figure 4). Beginning with the first infusion of milk, they tumble about their test containers, showing fragments of both ingestive and non-ingestive behavior patterns, while avidly mouthing and probing the floor and corners of the test container. When we first observed this behavioral response to diet infusion, because it appeared positive in nature, we speculated that it represented the functioning of an undifferentiated reward or reinforcement system. Support for the reward notion came from studies indicating that milk infusions and milk-induced excitement would produce appetitive operant and appetitive classical conditioning in newborn pups (e.g. Figure 3; also Johanson, Hall & Polefrone, 1984). This demonstration oflearning also suggested that, in Teitelbaum's sense (1966), early ingestive behavior and its accompanying affect could be considered 'motivated'. Thus, by infusing diet into the mouths of neonates, we could study the earliest ingestive responses of young rats, and also that we had access to a primitive system in which to explore the development of motivation.

Before die! infu sion

With di et infu si on s

FIGURE 4. Behavioral activation shown by a food-deprived, 3-day-old pup in response to oral infusions of milk. Pups mouth and probe the floor and become vigorously active, locomoting, rolling, and curling as well as showing numerous other responses. Milk infusions seem to trigger most of the behavioral responses in pups' repertoires (from Hall, 1979).

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INGESTIVE DEVELOPMENT

b. External Determinants The importance of temperature

Infant rats exhibit independent ingestion only when tested in a warm ambience (accomplished by adjusting our incubators to 33°C). Perceived temperature appears to playa permissive role for early ingestion and its accompanying excitement. A pup tested at room temperature, even if food-deprived, will refuse to consume infused solutions. The same pup, placed in an incubator warmed to nest temperature will, moments after refusing diet in a cooler environment, vigorously ingest the infused solution and become active. This effect of temperature depends on pups' immediate perception of ambient temperature and not core temperature (Johanson & Hall, 1980). It was the discovery of this thermal constraint on early feeding that has permitted the study of early ingestion independent of the mother and suckling (see Wirth & Epstein, 1976; the importance of warmth for ingestion in older pups was shown by Almli, 1973). Prior to this time, it had been felt that rat pups were not willing to feed independent of suckling until they were about 2 weeks of age. Once the importance of warmth was recognized, it was possible to show that neonates would not only ingest orally-infused diets, but would consume (in a deprivation-related manner) solutions spread on the floor of their warm test containers. In fact, young pups would even consume significant amounts of semi-solid rat chow mash (Figure 5). Early taste responsiveness

Shortly after birth, rat pups differentially respond to some tastes. In particular, their ingestive responses can be modulated by varying the sucrose or salt content of infused solutions. Further, differential behavioral responses to bitter solutions have been shown (Ganchrow, Steiner & Canetto, in press; and very strong bitter solutions can reduce intake, Johanson & Shapiro, 1983). But normal preference/aversion response functions and active rejection of orally infused solutions do not develop until later.

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FIGURE 5. Intake measured in an oral infusion test (a), (from Hall, 1979) or in a test of ingestion from the floor (b), (from Hall & Bryan, 1980). Pups were 1-6 davs of age and 1-24 h deprived. Intake was expressed either as a percentage of the infusion lea), a lO-min test), or as a percentage of body weight «b), a 30-min test).

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c. Internal Determinants

Control of early ingestion

In newborn pups, deprivation increases intake (Figure 5, Hall, 1979; Hall & Bryan, 1980), and the subsequent termination of ingestion has behavioral parallels to the satiety sequence of adult animals (Antin, Gibbs, Holt, Young & Smith, 1975). Moreover, gastric preloads suppress ingestion in both oral infusion feeding tests and tests of diet ingestion from the floor (Hall & Bruno, 1984). Thus, there are intake controls in the pup that in some ways resemble those of the adult. Analyses ofthe nature of the intake controls, though, reveal a simplicity and an apparent absence of some physiological determinants of ingestion typical of adults. In fact, in very young rats, there are only two specifically demonstrated controls of early independent ingestion: degree of gastric filling and hydrational status. Gastric Jactors

Attainment of a certain level of gastric fill appears to terminate intake, either for ingestion following deprivation, or following nutritive and non-nutritive gastric loads. This point is perhaps best demonstrated by recent studies utilizing a pyloric noose in 6day-old pups (Phifer, Sikes & Hall, Note 2). When ingested diet is trapped in a pup's stomach by activating the noose and preventing stomach emptying and absorption, pups consume less diet than when ingested solutions exit the stomach normally (Figure 6 a). Delivering a gastric preload after closure of the noose, but before an ingestion test, produces a reduction in intake that equals the volume of the load. Finally, the volume of the stomach at the termination of intake does not differ between pups ingesting normally (open nooses), pups ingesting normally after a gastric preload (open nooses), or in loaded or non-loaded pups with a closed pyloric noose (Figure 6 b). That is, when a young pup stops eating in each of these situations, it stops after having arrived at the same gastric volume. The presence of food in the intestine (i.e. the 'open noose' condition) adds no further inhibition. Removal of the gastric signal in pups that have

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FIGURE 6. (a). Intake as a percentage of body weight (± SEM).,for pups with a stomach noose that was either open or closed (blocking emptying) and that had received or not received a 5% bodyweight load of milk 1 h before testing (the noose was closed or not, just before the load). (b). Stomach volumes at the termination of ingestion in the same animals (from Phifer, Sikes & Hall, Note 2).

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ingested to satiety, by draining stomach contents through a fistula, results in renewed vigorous ingestion. A volume-based gastric control is thus a sufficient explanation for the termination of intake in young pups. No postgastric or postabsorptive control need be posited. Further, gastric distension appears to be necessary for termination of intake, since pups' 'sham' ingesting will continue to consume diet for extended periods (Phifer et a/., Note 2). Additional controls might still exist, but they have not yet been shown to provide a signal that adds to the gastric distension signal. This point was also made in a series of studies of 6-day-old pups using various load solutions and various ingestive tests (Hall & Bruno, 1984). Nutritive aspects of a loaded solution added no additional inhibition of intake beyond that accounted for by the gastric distension it produced. Stomach signals appear to be carried over vagal and splanchnic afferents, since vagotomized and cervically sectioned pups show reduced inhibition of feeding in an oral infusion test (Lorenz, Ellis & Epstein, 1982).

Other stimuli If there is some characteristic of deprivation other than gastric emptiness (or dehydration) that could lead to increased intake, it has not been identified. No acute nutritional or metabolic stimulus that has been tested increases ingestion in young pups. For example, despite the efforts of several labs, glucoprivation has not been shown to influence feeding before 3 weeks of age (see below). This absence of a metabolic effect on ingestion does not result from an inability of pups to increase consumption, or from an absence of neural mechanisms that can produce ingestion. Intake is increased at 10 days, for example, in response to central injections of norepinephrine (Ellis, Axt & Epstein, 1984).

H ydrational stimuli In contrast to the absence of metabolically elicited feeding, dehydration (either extracellular or cellular) is a potent stimulus for early ingestion in pups (Bruno, 1981; Wirth & Epstein, 1976). Angiotension, which is released in response to extracellular dehydration, is also a potent stimulus (when it is administered centrally) for ingestion in pups older than 4 days of age (Ellis et al., 1984; Misantone, Ellis & Epstein, 1980). Since deprivation in pups (i.e. from the mother and milk) invariably produces a profound dehydration (Friedman, 1975), dehydration probably contributes to the ingestive stimulus following deprivation. The importance of dehydration to the deprivation stimulus is revealed by the fact that water loads markedly reduce intake after deprivation, even after the water has been permitted to empty the stomach (Hall & Bruno, 1984). This inhibition of ingestion by water loads is in contrast to their stimulating effect on intake in food-deprived adults (Hsiao & Trankina, 1969). Thus, at this point, our simplest account for early ingestion is that it is mediated by hydrational status and degree of stomach filling (with presumably a pa rticular level of gastric fill being adequate to stop ingestion at a particular level of dehydration). From this perspective it is clear that distinguishing between early feeding and early drinking may be inappropriate. In fact, the differentiation of hunger and thirst becomes apparent only later in development. For this reason, here and elsewhere I speak of early 'ingestion' rather than feeding or drinking.

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4. SUBSEQUENT MILESTONES IN THE DEVELOPMENT OF INDEPENDENT INGESTION

a. Behavioral Organization Directed ingestive responding

As pups grow older, the diffuse excitement that characterizes ingestive responding by young, deprived pups is replaced by specific and directed ingestive behaviors. This shift in directedness of responding is an obvious and fascinating aspect of behavioral development. After 6 days of age, rather than exhibiting excitement when fed, deprived pups simply place their mouths on the floor beneath them and vigorously lap and mouth. Infusions seem to stimulate behavior specifically ingestive in nature. In fact, licking seems to be focused on one spot, as if pups imagined they were ingesting from a small puddle in front of them. This emergence of directed feeding has also been demonstrated by comparing intake when diet is spread over the entire floor vs. intake when diet is localized to a fraction of the floor surface. Through 6 days of age, pups consume only a fractional amount of the available solution when it is restricted in distribution, but by 12 days of age pups are capable of consuming just as much from a localized source as when diet is spread over the entire floor. So pups become able to orient, direct, and maintain their ingestive responding to a discrete source. This improvement in ingestion can also be viewed as an extension into the environment of pups' ingestive competence. From this perspective, the fundamental components of ingestion (along with some systems for their modulation) are present from birth, but effective environmental orientation emerges at a later age.

Internalization of reward

We hypothesized: (1) that the excitement shown by young pups was externalized evidence of the operation of an undifferentiated reward or reinforcement system; and (2) that as this system developed, its functions became internalized, subject to various inhibitory controls, and directed (perhaps as a result of maturation of specific inhibitory circuitry; e.g. adult-like cortical activity emerges at about this time, Hicks & D'Amato, 1975). Convergent evidence of the developmental organization and internalization of reward systems has been provided. Having first shown that pups would learn an operant response (similar to the milk-infusion reward situation) in order to receive electrical stimulation of their medial forebrain bundle (MFB; Moran, Lew & Blass, 1981), Moran, Schwartz and Blass (1983) went on to trace the behavioral responsiveness to stimulation of the MFB when pups were simply placed in an open field. Young pups became generally active and emitted many types of responses, resembling in many ways the generalized activation seen during milk infusions. Paralleling the change in response to milk infusions, as pups grew older, behavioral responding to MFB stimulation became "more organized and focused around a particular motivational system". At 15 days of age, at the parameters used, pups no longer showed a response to MFB stimulation, though they would work for MFB reward. These data revealing internalization of reward were interpreted in terms of the development of central inhibitory systems. Evidence that it might be cortical inhibition came from the demonstration that, in microencephalic pups with severe cortical hypoplasia, generalized excitement persisted through 15 days of age (Moran, Sanberg & Coyle, 1983).

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Weaning Normally, the principal landmark in the behavioral maturation of ingestive behavior is the shift from suckling to independent feeding. This transition is a gradual one that occurs from about 16 to 30 days of age (Babicky, Parizek, Ostadalova & Kolar, 1973), depending on housing and rearing conditions. Although weaning represents a major hurdle, and a fascinating one, our system for study of ingestive behavior tends to de-emphasize it in favor of tracing the continuity of pups' intrinsic ingestive response systems. For pups, abandoning suckling and taking up feeding is a process that partly represents achievements in ingestive system development, but also represents many other developmental accomplishments (e.g. social independence from the mother). b. Ex ternal Determinants Warmth to social comfort At the same time that the pup is becoming more competent in its ingestive behavior, the conditions under which ingestion occurs are becoming more constrained. Threeday-old pups require only a warm environment to ingest, but by 6 days of age familiar odors also influence ingestive responding. At 12 days of age, ingestive responding is influenced by temperature, familiar odor, and familiar tactile, visual, and auditory cues (e.g. those provided by sibling presence). These findings suggest that external controls progress from thermal to social (Johanson & Hall, 1980, 1981). These changes in the external control of ingestion undoubtedly depend partially on maturation of sensory systems (Alberts, 1984) and have been found in other domains of behavior as well as ingestion (e.g., huddling. Alberts, 1978; learning, Smith & Spear, 1980; also, Hofer, 1978). External modulation of ingestion achieves exaggerated importance in 15-dayold pups. These animals, at the verge of natural weaning, are the most easily distracted, the most reactive to the novelty of our ingestive test situations, and the least willing to feed of pups of any age. Even deprivation-related increases in ingestion are difficult to . obtain. This reactivity (and its reduction by familiar cues) parallels that reported for , other test situations (Campbell & Raksin, 1978). It diminishes by 20 days of age when pups seem more willing to feed and are less distract able. Any analysis of the development of ingestion must take into account this changing reactivity, which influences and interacts with all measures of ingestion. The adaptive importance of social cues as feeding determinants is ultimately expressed in the natural weaning process, where it has been demonstrated that pups initially feed at the same sites as siblings and con specifics (Galef, 1982; Galef & Clark, 1971, 1972). Indeed, even for adults, social cues have a potent influence over food selection (Galef, 1980). Pups' earlier reluctance to feed (i.e. at 15 days) may prevent premature weaning at a time when they have developed the dentition necessary for the ingestion of solid food, but are only just beginning to possess the appropriate gastrointestinal physiology (Henning, 1981). The relationship between the systems responsible for the early thermal control of ingestion (and other behaviors) and those representing more social control remains an interesting and open issue. The same basic system may subserve all sensory modulations of ingestive and other behaviors (i.e. a system that might be considered a "safety", "security", "comfort", or "familiarity" system); with the achievement of control over behavior by an increasing range of external stimuli involving specific experiences (see Rosenblatt, 1983). Findings from Alberts' lab in~icate experience could playa role

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in establishing temperature/odor relationships (Alberts & May, 1984). Or, the various influences over ingestion and other behaviors may be achieved in different manners. It seems to me important to identify mechanisms and substrates of these sensory modulators of behavior. Maturation of gustatory responsiveness

Pups show behavioral discrimination of sweet, bitter, salty, and acidic solutions shortly after birth (Hall & 1lryan, 1981; Ganchrow et ai., in press; Johanson & Shapiro, 1983), and there is evidence for underlying neural discrimination (e.g. Hill & Almli, 1979,1980; Ferrel, Mistretta & Bradley, 1981). Nonetheless, discrimination in terms of intake (e.g. preference and aversion functions) and adult-typical behavioral responses (e.g. Grill & Norgren, 1978) is slower to develop (Hall & Bryan, 1981). For example, concentration of sucrose in solutions does not affect intake until 6 days of age, and moderate concentrations of quinine do not depress intake below the level of water until 9 days of age (Figure 7). Characteristic rejection responses to quinine solutions of moderate concentrations do not appear until 12 days of age (Figure 8; Hall & Bryan, 1981; Grill & Norgren, 1978). Pups will reject solutions at an earlier age, as evidenced by rejection of hypertonic saline, but such rejection may be trigeminally mediated, and thus not represent pure gustatory aversion. Adult-typical salt preference is slow to mature (Midkiff & Bernstein, 1983; Moe, in press) with an insensitivity to salt evidenced by an early preference for higher concentrations. The maturation of gustatory function is probably partly due to receptor development, since the number of mature taste pores (and presumably receptors) increases impressively from birth for several weeks (Mistretta, 1981). As with the thermal/social control of early ingestion, the contribution to ingestive behavior made by gustatory competence must be considered in the developmental analysis of ingestion. Such considerations are particularly important in analyses where discrimination between two diets has interpretive significance (e.g. comparing thirst and hunger, see below). In studies with very young pups, the question must always be asked: what might these animals be reasonably expected to discriminate given their immature gustatory system?

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FIGURE 8. Characteristic aversion responses (chin-scraping and paw-pushing) shown to quinine infusions only by pups 12 days of age and older to quinine infusion (from Hall & Bryan, 1981 ).

c. Internal Determinants Gastric and nutritive factors The degree of gastric fill (or a related parameter such as intragastric pressure or rate of gastric filling) undoubtedly remains an important signal for intake termination into adulthood (Davis & Campbell, 1973; Deutsch, Young & Kalogeris, 1978; Kraly, Carty & Smith, 1978). Based on our own studies of the effects of gastric loads, it appears that distension (produced with non-nutritive loads) inhibits intake through at least 20 days of age. However, at 15 days of age, nutritive loads of glucose decrease intake to a greater degree than non-nutritive loads (Table 2). At this age, intake after nutritive loads of glucose is also terminated with less gastric fill than with non-nutritive loads (Hall, Phifer & Browde, Note 3). This finding suggests an onset of function of an inhibitory signal for intake termination that is not based solely on pregastric or gastric volume factors. At this point, we do not know if the signal is pre or postabsorptive, or even postgastric (e.g. there could be a developing gastric chemosensitivity). However, nutritive effects could be hormonally mediated. We have found, for example, that the putative satiety hormones, cholecystokinin (CCK) and bombesin, specifically inhibit ingestion in pups at 15 days of age (Phifer & Hall, 1984). Goldrich, Robinson, McH ugh & Moran (1984) have shown that intake in pups as young as 1 day of age can be depressed by CCK. We too found suppression in younger pups, but have also found that pups treated with CCK stop ingesting with smaller amounts of food in their stomachs. Because distension entirely accounts for the inhibition of intake in younger pups with or without gastric loads, it is not likely that the complete receptor/effector system for CCK action is functional at these ages. The early suppression of intake may reflect only that CCK receptors (specific to feeding, or nonspecific) are present in the system, not that the endogenous ligand is available and active. This issue is complicated by the fact that the site of action of CCK in the ingestive sequence of rats of different ages has not been identified. A considerable effort has been invested in studying the inhibitory controls of suckling, particularly using preload techniques (Anika, 1983; Drewett & Cordall, 1976; Friedman, 1975; Geiselman, Vanderweele, Dray, Ewing & Cryder-Mooney, 1980; Henning, Chang & Gisel, 1979; Houpt & Epstein, 1973; Houpt & Houpt, 1975; 1979; Lal, 1984; Lorenz, 1983; Lorenz, Ellis & Epstein, 1982). I have not discussed these findings here because I do not believe they bear directly on the emergence of independent ingestive behavior in the first 2 weeks of life. As weaning approaches and suckling is waning. it becomes more like feeding (see Hall & Williams, 1983); but before

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TABLE 2 Intake volumes (% body weight) in 30 min infusion tests following 5% body weight intragastric preloadsa

Loads Sham

Salineb

Glucose c

6-day-olds SEM

6·4 (0·6)

5·5 (0·3)

5·2 (0·7)

15-day-olds SEM

4·4 (0·6)

3·8 (0·5)

1·4 (0·5)

a2h delay following loads. bO·15M NaC!. cO·6M glucose. n=8.

that time it is difficult to relate effects on suckling to later feeding and drinking. Manipulations that affect suckling can have similar or very different effects on independent ingestion (e.g. Epstein, 1984; Raskin & Campbell, 1981). This is, in fact, one argument for the notion that the systems are different. The differences are worth understanding and the controls of suckling intake an interesting area for study, but I refer the interested reader to the thorough reviews of Blass, Hall & Teicher (1979), Drewett (1978), Epstein (1976 and in press), and Henning (1981). Metabolic signals for ingestion

One of the best documented milestones in the development of independent ingestive behavior is the onset of glucoprivic feeding. It is well documented because of the earlier attractiveness of the 'glucostatic' hypothesis for feeding (Mayer, 1955) and because it does not emerge until weaning, when independent ingestion has been more typically studied. Several laboratories have shown that pups do not respond to glucoprivation (produced by 2-DG or insulin injection) with increased ingestion until they are at least 20 days of age (e.g. Houpt & Epstein, 1973; Lytle, Moorcraft & Campbell, 1971). These stimuli do appear to have adult-typical physiological effects in young pups, e.g. 2-DG produced pronounced hyperglycemia (Houpt & Epstein, 1973). Using several types of independent ingestion tests, and several types of glucoprivic stimuli (2-DG, insulin, and 5-TG), John Bruno and I (unpublished observations) were not able to elicit increased ingestion in pups until after 15 days of age. There are several reasons why pups might be insensitive to changes in glucose level (or arterio-venous differences, or other aspects of glucose utilization) early in development. The primary one is that young pups depend on ketones as well as glucose as a metabolic fuel (Hawkins, Williamson & Krebs, 1971). Thus reducing glucose availability may not be as important to pups as to adults. Insulin administration, however, which could be expected to produce both hypoketonemia and hypoglycemia in young pups, does not affect early ingestion (either suckling or independent feeding). Moreover, preloads of either glucose or hydroxybutyrate have no suppressive effect on intake until 15 days of age (Hall et al., Note 3). These lack of effects seem to rule out the function of many types of early metabolic controls of ingestion in short-term tests of indS;!pendent ingestion. While these data are discouraging with respect to finding a metabolic stimulus for early feeding, they are consistent with the notion that glucoprivic control systems may be

INGESTIVE DEVELOPMENT

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emergency controls of feeding in rats, and are not part of the fundamental mechanisms for initiation and termination of ingestion (e.g. Friedman & Stricker, 1976; Kraly & Blass, 1974; Smith, Gibbs & Stromayer, 1972; Stricker, 1984). The absence of effects of glucoprivation on ingestion in pups also reflects the fact that studies of early control of ingestion are not likely to provide information on long-term regulatory aspects of energy balance or weight regulation. Such long-term controls are mechanisms that the developing animal may appropriately and adaptively lack. It appears that distension and hydration may be the only determinants of intake during the first week, and further controls are added later. I suggest this as a provisional account of the development of independent ingestion. Considerable additional study of post-gastric, post-absorptive, and metabolic controls of early independent ingestion is still required (in particular, work with diets and preloads having other nutritional characteristics is needed). The differentiation offeeding and drinking With gastric fill and fluid balance as the major determinants of independent ingestion in infant rats, early ingestion is best conceptualized as undifferentiated with respect to hunger and thirst. Results from my laboratory indicate that very young pups do not discriminate ingested solutions on the basis of whether they are dehydrated or deprived (see also, Bruno, 1981). Epstein and his coworkers (Ellis et ai., 1984; Misantone et al., 1980) have provided a clear documentation of the emergence of such discrimination. Using a "pre-satiation" technique, which gives their approach considerable sensitivity, they have shown that the milk/water discrimination for angiotensin-stimulated ingestion does not develop until 8 days of age, and for norepinephrine-stimulated ingestion not until 10 days of age. The most extreme and convincing example of the adult's differentiation between feeding and drinking occurs when dehydrated animals refuse food (dehydrationinduced anorexia). This phenomenon does not emerge in rat pups until 20 days of age (Bruno, 1981; Bruno & Hall, 1982; and here, its emergence in independent feeding parallels its emergence in suckling, Bruno, Cragmyle & Blass, 1982). For example, through 15 days of age, rat pups increase their intake of milk after dehydration, but, from 20 days, dehydratjon reduces milk intake. In a converse fashion, in young animals that are deprived, intake of all solutions is inhibited by rehydration with water preloads. By 15 days of age, though, water loads begin to take on their adult-typical effect of increasing food intake after deprivation (Hall et a!., Note 3). Thus several types of evidence indicate that differences between feeding and drinking develop after birth and before weaning. Differences in the timing of emergence of these distinctions may bear on the processes that distinguish hunger and thirst. Later emerging components of ingestion My focus here has been on developments in the first 3--4 weeks oflife. I don't mean to imply that interesting things do not happen later. Indeed, as I've suggested, bodyweight regulatory systems probably develop after weaning. They may depend on physiological events that occur with weaning (e.g. Henning, 1981) or later events of puberty (e.g. Wade, 1972). Further, the post-weaning period is the time when rats normally learn about the consequences of independent feeding. Limited evidence indicates that such experiences can also be important in determining how ingestion is initiated and terminated (e.g. Booth, Stoloff & Nichols, 1974; see Weingarten this issue), and in determining food

w.

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G. HALL

choice (the role of experience in the development of feeding has been better studied in species other than rats, e.g. chickens, Hogan, 1973; guinea pigs, Reisbeck, 1973; doves, Graf, Silver & Balsam, in press). Moreover, the postweaning period represents the first opportunity for conditioning of components of appetite and satiety. Whether pups' developmental status is critical in determining the magnitude of experiential effects is an open question (i.e. do young animals learn the same kinds of things as adults, or are there special consequences of early feeding experience?). Pups certainly do not need to learn how to feed-since they can eat at birth and since deprivation of ingestive experience for virtually the entire suckling period (by artificial rearing using an intragastric feeding system) does not prevent the normal emergence offeeding on solid food (but it does disrupt suckling; Hall, 1975; Stoloff, Kenny, Blass & Hall, 1980).

5.

THE REVELA nONS OF DEVELOPMENT

The work described above is based on the implicit assumption that by studying a system from its early existence, we can gain insight into its organization. This "developmental strategy" reflects the optimistic notion that the system of the infant is simple (or at least different) and, thus, more easily understood. In many ways, early simplicity now seems a reasonable assumption with respect to rat ingestive behavior. A second advantage of developmental analysis is that one can be fairly certain that neonatal pups have had relatively little experience with independent ingestion at the time of testing. However, the validity of the developmental strategy for understanding adult systems depends on a continuity between the system being studied at an early age and the system of interest in older animals (Oppenheim, 1981). This criterion of continuity between infant and adult ingestion is not met by suckling, but most evidence supports continuity between early independent ingestion (as described here) and adult feeding (e.g. Hall & Williams, 1983). In addition to increasing our understanding of a system by revealing the ontogenetic emergence of its components, developmental analysis can contribute other types of revelations about the organization of early behavior. These revelations occur because developing animals are different from adults, require different methodological approaches, and demand fresh observational perspectives. Thus, while I have called attention above to our burgeoning understanding of the programmatic events in ingestive development, such a presentation still misses much of the excitement, surprise, and inspiration that can be derived from ontogenetic analysis. In my own work, the best example of a revelation resulting from the developmental approach was the finding that young rats would not only actively ingest, but that feeding dramatically excited them. I've described some of the implications of this behavioral activation phenomena, but I have not noted one of its major features. While nutritional deprivation is partly responsible for the activation shown by young, deprived pups when they are fed, it is only part ofthe story. Deprivation from maternal care (and normal mother-infant interactions) is also important for behavioral activation. The two factors, nutritional deprivation and loss of maternal care interact synergistically to produce behaviorally reactive pups. This complex control of reactivity is best demonstrated by experiments in which pups were deprived in one of several ways: (1) by placing them in a warm moist incubator (our typical deprivation treatment); (2) by leaving them with a mother that was no longer lactating because her pups had been removed several days before (allowing an opportunity to interact with a mother, receive normal maternal care, and suckle, but not receive milk); or (3) by

349

INGESTIVE DEVELOPMENT

Ica\'ing them with a normally lactating mother (our non-deprived control condition). When animals deprived in manners 1 and 2 were subsequently tested in an infusion feeding situation, both of these groups that were deprived of nutrition showed equally high intake of milk compared to the nondeprived group (Figure 9 a; Bornstein, Terry, Browde, Assimon & Hall, Note 4). However, pups left with a non-lactating mother (group 2) had the same low level of activity as non-deprived pups (group 3; Figure 9 b). Rather than become excited by milk infusions, group 2 simply mouthed and ingested the infused diet. Thus, the affective reaction to milk infusions, one that seems to represent the functioning of a primitive reward system, depends on some component of maternal deprivation. We know that the maternal component is not simply the experience of suckling, because maternal care provided by females with undeveloped nipples (induced maternal behavior; e.g. Rosenblatt, 1967) is as effective in reducing activity as maternal care provided by a normal mother. Food deprivation is also required because pups deprived of both food and maternal care do not become active if they receive gastric loads before testing (Hall & Bruno, 1984; Phifer et at., Note 2). This activation phenomenon, which is only observed in the behavior of young animals, calls attention to the interaction of two separate systems necessary for excitement and, presumably, reinforcement. These interacting systems may be the foundation for foodrelated reward systems in the adult. At this point, their effects on arousal provide an indication of possible soun:es for multiple modulation of the rewarding properties of food. 6.

WHAT'S MISSING?

Using the Early Independent Ingestion Approach

In a descriptive sense, we've made a good start at mapping the ontogeny of independent ingestion and in devising paradigms to study the process (Figure 10). The

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FIGURE 9. Intake (a) and activity (b) scores for pups that were left with a normally-lactating mother (ND, non-deprived), with a mother that was not lactating (S, surrogate), or in an incubator (D, deprived) during the 24-h period preceding infusion tests. Intake in a lO-min test is expressed as a percentage of the infusion, activity as the total score (from our rating system) for the test (from Bornstein et aI., Note 4).

350

W. G. HALL Approxlmote age (days)

Behavior

Externol determinants

Ingestion with generolized activity

1

Directed Ingestion

j Differentiation of feeding and drinking

Temperature dependence

(Some toste discrimlnotlon)

J l

Olfoctory modulotion

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1 1 1 1

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7

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Glucoprivation

J

FIGURE 10. A preliminary outline of changes that occur in the organization of independent ingestive behavior in the first three weeks of the rat's life.

presence of an early, independent ingestive system is of empirical utility in addressing certain kinds of questions about the nature offeeding. These include the identification of individual controls of ingestive behavior as each emerges. As onsets of function become better understood, we will be in a position to exploit them. First, we can study early-emerging ingestive controls in the absence of other controls. Then the nature of their interaction with systems that are added during ontogeny can be worked out. Because pups are relatively naive when tested in our independent ingestion paradigm, they are likely to initiate and terminate ingestion on the basis of straightforward effects of internal and external signals, and the results are not likely to be confounded by previous learning about feeding (as they could be in older animals). Specific examples of issues whose resolution would be very informative are: (a) Are hydrational status and gastric fill the sole determinants of early ingestion? (b) On which components of the ingestive sequence do they act, and do these change with age? (c) What is the nature of the first additional control? What others follow? And, on what components in the sequence do they act? (d) What is the relationship between external and internal determinants? Is their manner of action one that has significance for adult ingestion? (e) Why is sensory deprivation important for the affective response; does its role shift when affect is internalized? While our analyses have focused on pups during the first three weeks of life, they make for a straightforward comparison to ingestion in older animals. For example, feeding from a restricted source of food on the test container floor is just a simple version of an adult feeding situation. Thus, there is a natural continuity of measures of ingestion in early development into later life (infusion tests have been shown to have their utility in adults as well, Grill & Norgren, 1978). The study of early independent ingestive behavior will also be important in identifying the neural mechanisms of ingestive behavior. First, the ingestive system can

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be studied when it is simpler, making it easier to relate emerging ingestive responscs and controls to their neural basis. More importantly, the emergence of new functions can be related to events in neural maturation.

Other Strategies

Despite my enthusiasm for the approach and methods described here, there are important questions about the ontogeny of ingestion that they do not address. Answers to these questions need to be approached differently (or at later ages), but will be equally informative about the make-up of ingestive systcms in adult animals. To date they have received only slight attention. Feeding normally emerges as pups give up suckling. Experiences both of weaning (e.g. mother-infant interactions) and those during the ingestion of the first normal meals undoubtedly contribute in important ways to later feeding. At the very least, they may help stimulate normal physiological and gastrointestinal development (e.g. Henning, 1981; Koldovsky, 1985). OUf understanding of the causes of weaning is limited (see Alberts, 1984; Blake & Henning, 1983; Blake, Okuhara & Henning, 1984; Stoloff & Blass, 1983; Williams, Hall & Rosenblatt, 1980). Our appreciation of the significance of first feeding experiences is poor. Major reorganizations of behavior occur at weaning: For example, discrete meal-taking emerges, the period of feeding becomes nocturnal (Levin & Stern, 1975), and prandial drinking develops (Kissileff, 1971). How do the experiences of eating and its post-ingestive consequences contribute to these changes in the organization of ingestive behavior and control and regulation of subsequent feeding? How are experiences related to feeding integrated with the factors that initiate and terminate ingestion? An understanding of the contribution of particular types of early ingestive experiences should make it possible to decipher the nature of the plastic or adaptive contribution to feeding control. Besides the importance of developing an understanding of weaning and the importance of ingestive experience occurring at about this time, it is reasonable to ask what earlier suckling experiences may contribute to the development of feeding. While we have argued that early suckling behavior has little in common with other ingestive systems that are present at the time or with later ingestion, it is the case that during the last week or so of suckling it becomes more like feeding (e.g. Hall & Williams, 1983). The pup seems to begin to view the mother as a source offood and both nipple attachment and intake are controlled in an adult-like manner. It is reasonable to ask whether suckling has some representation in later behavior, or specifically, in later feeding behavior. There is certainly indication that taste and olfactory experiences during suckling can make at least transient contributions to later food preferences (Capretta & Rawls, 1974; Galef & Clark, 1972; Galef & Henderson, 1972; Galef & Sherry, 1973) as well as affecting intake during suckling (Terry, Craft & Johanson, 1983). Moreover, it is worth considering how suckling experiences, ingestive or not, are represented in later behavior (e.g. Cramer, 1982; Fillion & Blass, 1984). Beyond these normally occurring ingestive experiences, it is possible to program specific types of early ingestive experiences in developing pups (e.g. using infusion-feeding approaches or artificial rearing). Such investigations, while not likely to bear on the normal developmental process, may provide revealing information about the organization of the ingestive system at any age.

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W. G. HALL

7. A FINAL WORD ON ONTOGENY

This group of articles on feeding development will perhaps call attention to a truth about ingestive behavior that is on the one hand obvious but, on the other, often ignored. Feeding, like all behavioral systems, does not have a static "adult" form. Throughout an animal's life, ingestion undergoes changes (e.g. late ones in cortical control, Kolb & Nonneman, 1976) and is part of the active interaction of genome and environment. Ingestion, at any stage, is a product of ontogenetic processes. I have focused primarily on a set of methods and strategies for studying ingestive organization during the first few weeks of life. For reasons I have discussed (simplicity, lack of specific kinds of confounding experience, and the opportunity to relate behavioral development to neural development), I view this period as a particularly useful one for developmental analysis. But development does not end at weaning, and developmentally-oriented analysis of ingestion throughout an animal's life is the most appropriate conceptual framework for understanding ingestion. REFERENCE NOTES

1. Terry, L. M. & Hall, W. G. Unpublished observations, 1984 2. Phifer, C. B., Sikes, C. R. & Hall, W. G., Control of intake in 6-day-old rat pups: Termination of intake by gastric fill, submitted. 3. Hall, W. G., Phifer, C. B. & Browde, J. A., Jr. The onset of nutritional controls of independent ingestion in infant rats. Paper in preparation. 4. Bornstein, B., Terry, L. M., Browde, 1. A., Jr., Assimon, S. A. & Hall, W. G. Sensory and nutritional contributions to rat pups' early activational response to ingestion. Submitted.

REFERENCES

Alberts, 1. R. Huddling by rat pups: Multisensory control of contact behavior. Journal of Comparative and Physiological Psychology, 1978,92,220-230. Alberts, J. R. Sensory-perceptual development in the Norway rat: A view toward comparative studies. In R. Kail & N. E: Spear (Eds.), Comparative perspectives on memory development. Pp. 65-101. New Jersey: Erlbaum, 1984. Alberts, 1. R. Early learning as an ontogenetic adaptation for ingestion by rats. Learning and Motivation, 1984, 15, 334-359. Alberts, J. R. & May, B. Nonnutritive, thermo tactile induction of filial huddling in rat pups. Developmental Psychobiology, 1984,17, 161-181. Almli, C. R. The ontogeny of the onset of drinking and plasma osmotic pressure regulation. Developmental Psychobiology, 1973,6, 147-158. Anika, S. M. Ontogeny of cholecystokinin satiety in rats. European Journal of Pharmacology, 1983,89,211-215. Anokhin, P. K. Systemogenesis as general regulator of brain development. Progress in Brain Research, 1964, 9, 54-87. Antin, 1., Gibbs, J., Holt, J., Young, R. C. & Smith, G. P. (1975) Cholecystokinin elicits the complete behavioral sequence of satiety in rats. Journal of Comparative and Physiological Psychology, 1975,89,784-790. Babicky, A., Parizek, 1., Ostadalova, I. & Kolar, J., Initial solid food intake and growth of young rats in nests of different sizes. Physiologia Bohemoslovenica, 1973, 22, 557-566. Blake, H. H. & Henning, S. J. Weaning in the rat: A study of hormonal influences. American Journal of Physiology, 1983, 244, R537-R543. Blake, H. H., Okuhara, C. T. & Henning, S. J. Role of dietary preferences in the weaning pattern of the rat. American Journal of Physiology, 1984,246, R96--RI01.

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Blass, E. M. & Cramer, C. P. Analogy and homology in the development of ingestive behavior. In A. R. Morrison & P. L. Strick (Eds), Changing concepts of the nervous system. Pp.503- 523. New York: Academic Press. Blass, E. M., Hall, W. G. & Teicher, M. H. The ontogeny of suckling and ingestive behaviors. Progress in Psychobiology and Physiological Psychology, 1979,8,243- 299. Booth, D. A., Stoloff, R. & Nicholls, 1. Dietary flavor acceptance in infant rats established by association with effects of nutrient composition. Physiological Psychology, 1974,2,313- 319. Brake, S. c., Sager, D. J., Sullivan, R. & Hofer, M. The role of intraoral and gastrointestinal cues in the control of sucking and milk consumption in rat pups. Developmental Psychobiology, 1982, 15, 529-541. Brake, S. c., Wolfson, V. & Hofer, M . A. Electrophysiological patterns associated with nonnutritive sucking in 11- 13-day old rat pups. Journal of Comparative and Physiological Psychology, 1979,93, 760-770. Bruno,1. P ., Development of drinking behavior in preweanling rats. Journal of Comparative and Physiological Psychology, 1981, 95, 1016-1027. Bruno, J. P., Craigmyle, L. S. & Blass, E. M. Dehydration inhibits suckling behavior in weanling rats. Journal of Comparative and Physiological Psychology, 1982,96,405-415. Bruno, J. P. & Hall, W. G. Olfactory contributions to dehydration-induced anorexia in weanling rats. Developmental Psychobiology, 1982,15,493-505. Campbell, B. A. & Raskin, L. A. Ontogeny of behavioral arousal: The role of environmental stimuli. Journal of Comparative and Physiological Psychology, 1978,92, 176-184. Capretta, P. J. & Rawls, L. H., III Establishment of flavor preferences in rats- Importance of nursing and weaning experience. Journal of Comparative and Physiological Psycholog y, 1974, 86, 670-673. Cramer, C. P. Are foraging strategies influenced by experience during suckling? Abstracts Annual Meeting, International Society for Developmental Psychobiology, p. 11, 1982. Davis, J. D . & Campbell, C. S. Peripheral control of meal size in the rat: Effect of sham feeding on meal size and drinking rate. Journal of Comparative and PhYSiological Psychology, 1973,83, 379- 387. Deutsch, J. A., Young, W. G. & Kalogeris, T. J. The stomach signals satiety. Science, 1978,201, 165-167. Drewett, R. F. The development of motivational systems. Progress in Brain Research, 1978,48, 407-417. Drewett, R. F. & Cordall, K. M . Control of feeding in suckling rats: effects of glucose and of osmotic stimuli. Physiology and Behavior, 1976, 16, 711-717. Ellis, S., Axt, K. & Epstein, A. N . The arousal of ingestive behaviors by the injection of chemical substances into the brain of the suckling rat. Journal of N euroscience, 1984,4, 945- 955. Epstein, A. N . Feeding and drinking in suckling rats. In D . Novin, W. Wyrwicka & G. A. Bray (Eds), Hunger: basic mechanisms and clinical implications. Pp. 193- 202. New York: Raven, 1976. Epstein, A. N. The ontogeny of neurochemical systems for control of feeding and drinking. Proceedings of the Society for Experimental Biology and M edicine, 1984, 175,127-134. Epstein, A. N. The ontogeny of ingestive behaviors: Control of milk intake by suckling rats and the emergence of feeding and drinking at weaning. In R. Ritter, S. Ritter & c. D. Barnes (Eds), Neural and humoral controls offood intake. New York: Academic Press, in press. Ferrell, M . F., Mistretta, C. M . & Bradley, R. M. Chorda tympani taste responses during development in the rat. Journal of Comparative Neurology, 1981 , 198, 37-44. Fillion, T. J. & Blass, E. M. Infantile experience with suckling odors guides adult male sexual behavior. Abstracts, Annual Meeting, International Society for DevelopmentalPsychobiology, p. 36, 1984. Friedman, M. I. Some determinants of milk ingestion in suckling rats. Journal of Comparative and Physiological Psychology, 1975,89,636-647. Friedman, M. T. & Stricker, E. M. The physiological psychology of hunger: A physiological perspective. Psychological R eview, 1976,83,409-431. Galef, B. G., Jr. Diving for food: Analysis of a possible case of social learning in rats (Rattus norvegicus). Journal of Comparative and Physiological Psychology, 1980,94, 416-425.

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Galef, B. G., Jr. The development of flavor preferences in man and animals: The role of social and nonsocial factors. In R. N. Aslin, J. R. Alberts & M. R. Peterson (Eds), Development of perception: psychobiological perspectives Vo!' I. Pp. 411-431. New York: Academic Press, 1982. Galef, B. G., Jr. & Clark, M. M. Parent-offspring interactions determine the time and place of first ingestion of solid food by wild rat pups. Psycho nomic Science, 1971,25, 15-16. Galef, B. G., Jr. & Clark, M. M. Mother's milk and adult presence: Two factors determining initial dietary selection by weanling rats. Journal of Comparative and Physiological Psychology, 1972, 78, 220-225. Galef, B. G., Jr. & Henderson, P. W. Mother's milk: A determinant of the feeding preferences of rat pups. Journal of Comparative and Physiological Psychology, 1972, 78, 213-219. Galef, B. G., Jr. & Sherry, D. F. Mother's milk: A medium for the transmission of cues reflecting the flavor of mother's diet. Journal of Comparative and Physiological Psychology, 1973,83, 374-378. Ganchrow,1. R., Steiner, 1. E. & Canetto, S. Behavioral displays to gustatory stimuli in newborn rat pups. Developmental Psychobiology. In press. Geiselman, P. J. Vanderweele, D. A., Dray, S. M., Ewing, A. T. & Cryder-Mooney, E. Ontogeny of chemospecific control of ingestive behavior in the rat. Brain Research Bulletin, 1980, 5 (Supp!. 4), 37-42. Goldrich, M. S., Robinson, P. H. McHugh, P. R. & Moran, T. H. Cholecystokinin inhibition of independent milk ingestion in neonatal rats. Abstracts, Annual Meeting, International Society for Developmental Psychobiology, p.44, 1984. Graf,1. S., Balsam, P. D. & Silver, R. Associative factors and the development of pecking in the ring dove. Developmental Psychobiology. In press. Grill, H. 1. & Norgren, R. The taste reactivity test. II. Mimetic responses to gustatory stimuli in chronic thalamic and chronic decerebrate rats. Brain Research, 1978, 143,281-297. Hall, W. G. Weaning and growth of artificially reared rats. Science, 1975,190, 1313-1315. Hall, W. G. The ontogeny of feeding in rats. I. Ingestive and behavioral responses to oral infusions. Journal of Comparative and Physiological Psychology, 1979,93,977-1000. Hall, W. G. & Bruno, J. P. Inhibitory controls of ingestion in 6-day-old rat pups. Physiology and Behavior, 1984,32,831-841. Hall, W. G. & Bryan, T. E. The ontogeny of feeding in rats. II. Independent ingestive behavior. Journal of Comparative and Physiological Psychology, 1980, 94, 746-756. Hall, W. G. & Bryan, T. E. The ontogeny offeeding in rats. IV. Taste development as measured by intake and behavioral responses to oral infusions of sucrose and quinine. Journal of Comparative and Physiological Psychology, 1981, 95, 240-251. Hall, W. G. & Williams, C. L. Suckling isn't feeding, or is it? A search for developmental continuities. In J. S. Rosenblatt, R. A. Hinde, R. A. Beer & M. Busnell (Eds), Advances in the study of behavior Vol. 13. Pp. 219-254. New York: Academic Press, 1983. Hawkins, R. A., Williamson, D. H. & Krebs, H. A. Ketone-body utilization by adult and suckling rat brain in vivo. Biochemical Journal, 1971, 122, 13-18. Henning, S. 1. Postnatal development: coordination of feeding, digestion, and metabolism. American Journal of Physiology, 1981,241, GI99-G214. Henning, S. J., Chang, S.-S.P. & Gisel, E. G. Ontogeny of feeding controls in suckling and weanling rats. American Journal of Physiology, 1979, 237, RI87-RI91. Hicks, S. P. & D'Amato, C. J. Motor-sensory cortex-corticospinal system and developing locomotion and placing in rats. American Journal of Anatomy, 1975,143, 1-42. Hill, D. L. & Almli, C. R. Neural ontogeny of chorda tympani taste responses in the rat. Neuroscience Abstracts, 1979, 5, 128. Hill, D. L. & Almli, C. R. (1980) Ontogeny of chorda tympani nerve responses to gustatory stimuli in the rat. Brain Research, 1980, 197,27-38. Hogan, J. A. (1973) How young chicks learn to recognize food. In R. A. Hinde & J. StevensonHinde (Eds), Constraints on learning. London: Academic Press, 1973. Hofer, M. A. Hidden regulatory processes in early social relationships. In P. P. G. Bateson & P. H. Klopfer (Eds), Perspectives in ethology, Vo!. 3. Pp.135-163. New York: Plenum Press, 1978. Houpt, K. A. & Epstein, A. N. Ontogeny of controls of food intake in the rat: GI fill and glucoprivation. American Journal of Physiology, 1973,225, 58-66.

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