Hormonal and behavioral aspects of maternal care in the hamster: A review

Neuroscience & Biobehavioral Reviews, Vol. 4, pp. 1%26. Printed in the U.S.A.

Hormonal and Behavioral Aspects of Maternal Care in the Hamster: A R e v i e w I H A R O L D I. S I E G E L A N D J A Y S. R O S E N B L A T T

Institute o f A n i m a l Behavior, R u t g e r s - - T h e State University, N e w a r k , N e w Jersey 07102 Received 12 O c t o b e r 1979 SIEGEL, H. I. AND J. S. ROSENBLATT. Hormonal and behavioral aspects of maternal care in the hamster: A review. NEUROSCI. BIOBEHAV. REV. 4(1) 17-26, 1980.--This review covers a description of the maternal behavior cycle in the hamster and relationships between the endocrine system and prepanum changes in activity, aggression, sexual receptivity, and maternal care. Postpartum maternal behavior consists of the mother's "normal" cannibalism of some portion of her litter, the formation of a bond between mother and her young, the development of behavioral synchrony between the mother and her pups, and maternal aggression toward conspecifics. The maternal responses of virgin female, male, and juvenile animals are described and methodologicalconsiderations in the testing of both virgin and parturient animals are presented. Finally, a theoretical framework for considering the regulation of maternal care in the hamster is presented. Two main phases of regulation are proposed; an onset phase that originates prepertum and depends on the physiological conditons of pregnancy and a maintenance phase which provides for the continuation of maternal care during lactation and is based on both endogenous maternal factors and external litter-related stimuli. A transition period beginningat parturition facilitates the shift between the onset and maintenance phases. Maternal behavior Hamster Pregnancy Lactation Cannibalism Mother-youngbond Mother-litter synchrony Estrndiol Progesterone Prolactin Aggression Sexualreceptivity

INTEREST in the golden hamster for use in endocrinological and behavioral studies has increased dramatically in recent years. In particular, the endocrinology of pregnancy and maternal behavior have received an increased amount of attention. It seemed appropriate to us, therefore, to review these studies especially because previous reviews of parental behavior in laboratory mammals have concentrated either entirely or most heavily on the rat,mouse, and rabbit [17, 18, 25, 27, 29, 44]. The aim of this review is to critically survey the observational and experimental findings on maternal behavior and to examine the relevant endocrinologicai studies with respect to the golden hamster. As a general guide we have used our research and reviews [30,31] of maternal behavior and gestational endocrinology in the rat to organize the material under topics and to present a theoretical framework. Maternal behavior may be considered an outgrowth of the physiological conditions existing during gestation and at parturition. Our first topic is therefore concerned with behavioral changes occurring during pregnancy and with the onset of maternal behavior at the termination of pregnancy. Maternal behavior after parturition is a product of the female's maternal condition and the kind of stimulation she receives from her young. Our second topic is the relative contributions of these two factors in the postpartum pattern of maternal care. In the rat and mouse, studies on the maternal responses of nonpregnant animals have contributed to our understanding of maternal behavior as it normally occurs in

postparturient females. Studies on maternal behavior in nonpregnant hamsters is therefore the third topic to be covered and our fourth topic deals with the neural basis of maternal care in parturient and non-pregnant animals. It will be seen, during our review, that methodological differences among investigators play a large role in the different findings that are reported. Our fifth topic will review problems of methodology in the study of maternal behavior in the hamster. Finally, in the last section we shall attempt to organize the existing evidence on maternal behavior in the hamster into a theoretical framework. THE MATERNALBEHAVIORCYCLE

A Brief Description The duration of gestation and the timing of parturition are very precise in the hamster. Animals maintained on a 14 hr light: 10 hr dark photoperiod deliver an average of 6-9 pups during the morning of day 16 with a narrow range of variability in the onset of parturition [35]. The behavior of the hamster during delivery of the young is similar to that observed in other laboratory rodents. Parturition requires three hours or slightly less and takes place in the maternal nest, an elaboration of the sleeping nest which the mother begins to build several days after mating. The birth of each pup stimulates the mother to lick the amniotic fluids and consume the umbilical cord and placenta. Occasionally, the f'wst born pups begin to suckle before par-

1Written with the support of USPHS Grant MH-08604 to J. S. R. and a Biomedical Research Support Grant. The authors wish to thank Ms. Cynthia Banas for preparation of the illustration and Ms. Nancy Jachim for secretarial assistance. Publication No. 338 from the Institute of Animal Behavior, Rutgers--The State University, Newark, New Jersey.

Copyright © 1980 A N K H O International Inc.m0149-7634/80/010017-10501.50/0

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SIEGEL AND ROSENBLATT

turition is completed but most often active nursing begins some time after the entire litter is delivered. Also, on occasion, a pup is born outside of the nest and this increases the likelihood that the pup will be ignored [33]. For further descriptions of the birth process, the reader is referred to Rowell [33]. Under laboratory conditions, the early postpartum period is characterized by highly motivated parental behavior including nest building, retrieving, licking of the young, and long periods spent in the nest most often in a nursing position (crouching). The incidence and duration of these activities begins to decline around the end of the second week of lactation. During the third and fourth weeks, the mother changes her nest site, builds a smaller nest, no longer retrieves her young, and occasionally attacks the pups if theyattempt to nurse [32,33]. Weaning of the young signals the resumption of estrous cyclicity and the potential for a subsequent pregnancy. Unlike a number of other species, the hamster has no postpartum ovulation [11].

Hormone-Behavior Relationships during Pregnancy There are a number of significant changes in activity, aggression, lordosis and nest building which occur during gestation in the hamster. Among these changes, also, is the onset of maternal behavior during late gestation. Because the ovarian hormones and prolactin have been implicated in the control of each of these different kinds of behavior, the circulating levels of estradiol, progesterone, and prolactin during pregnancy are presented in Fig. 1. Also included in this figure are their levels during lactation which will be referred to in a later section of this paper. Attempts to correlate the frequency and intensity of specific items of behavior with circulating levels of particular hormones are sometimes difficult. As an example, during gestation measures of activity of animals in their home cages

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show decreases between days 4 and 5 and between days 9 and 10 in time spent in the nest and in sleeping [24]. Estradiol levels increase over these same intervals. However, increases in estradiol at least as large occur between days 6 and 7, l0 and 1 l, and 13 and 14 (Fig. l) when no significant changes in activity are noted. The failure to obtain more consistent correlations between estradiol and activity may be attributed to the methods used to measure the behavior and the hormones. While home cage observations showed fluctuations in a variety of behaviors, wheel running scores decreased steadily over pregnancy which may merely reflect a progressive increase in body weight. In addition, the behavioral measurements were taken for one hour each day during the dark phase of the diurnal light/dark cycle while blood samples were collected once daily during the light phase [ 1,2]. The display of aggressive behavior and sexual receptivity (lordosis behavior) among hamsters has been compared during various reproductive states [42]. Pregnant animals are more aggressive towards males than pseudopregnant (days 2, 6, and 8) and cycling females (days 2, 3, and 4). During pregnancy, aggression is higher on day 10 than on days 2, 6, and 14. Animals on day 10 of pregnancy in the Wise study correspond to animals on day 11 in the Baranczuk and Greenwald experiment on estradiol levels shown in Fig. 1. Although various investigators have reported different effects of ovarian steroids on female aggression [1220], the highest levels of aggressive behavior and estradiol are closely related. Lordosis behavior was only displayed during late pregnancy (days 10 and 14) although females were also tested during early pregnancy (days 2 and 6). Despite the fact that the mean duration of lordosis is not as long as it is during the estrous cycle, it is interesting that high levels of aggression and sexual receptivity occur on the same days. The hamster clearly depends on estrogen and progesterone for lordosis

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FIG. I. Circulating levels of estradiol, progesterone, and prolactin during pregnancy and lactation in the hamster. (Adapted from [t,2]).

MATERNAL BEHAVIOR IN HAMSTERS behavior [6] and days 10 and 14 are associated with relatively high levels of both of these steroids. More directly related to parental care is the initiation of maternal nest building which begins during pregnancy. Unlike some other rodents which build nests near term, the hamster begins nest building soon after mating [7,21]. When nest building is measured by removing the nest daily and weighing it, the quantity of nest material used begins to increase on day 4 of pregnancy and exceeds the highest levels found during the estrous cycle by day 6. It increases steadily thereafter until delivery [21]. The relationship between maternal nest building and steroids was examined in ovariectomized animals treated for 18 days with subcutaneous implants of estradiol and/or progesterone [26]. Only hamsters given large implants of both hormones showed a significant increase in the amount of straw they incorporated into their nests, equal to that shown by pregnant animals. Groups treated with either small implants of estradiol and progesterone or either hormone alone did not display an increase in nest building. Male hamsters castrated in adulthood and implanted with estrogen and progesterone showed a small increase in nest building compared to intact males with similar implants and both groups of males used significantly less straw than the estrogen- and progesterone-implanted, ovariectomized females. The sex difference in response to the steroid implants was not affected by neonatal castration in males or neonatal testosterone treatment in females.

Prepartum Maternal Responsiveness

The majority of virgin hamsters attack and cannibalize young pups. This is in contrast to parturient animals that are usually quite maternal. The change in responsiveness is related to some aspect of pregnancy and a f'trst step in determining the underlying hormonal basis requires that the period during pregnancy when this change occurs be examined. Pregnant hamsters that wers tested within 24 hr of parturition exhibited attack and canniablism that was intermediate between that of virgin and recently parturient animals [23]. In these tests, three foster pups were placed directly into the nest of each of the animals for a single 15 rain test. Only one of eight parturient animals was observed eating a pup whereas all eight virgins attacked and killed all of the pups. Further, 5 of 8 of the lactating females displayed nursing behavior and all of them were observed nest building but none of the virgins showed nursing behavior and 5 of 8 showed nest building. The pregnant animals typically attacked and killed one or two of the pups and then behaved maternally toward the remaining young. Nursing behavior was shown by 5 of 9 pregnant animals and all of them were nest building during the test. In a recent study aimed at delineating more precisely the onset of maternal care [35], hamsters were tested at specified intervals beginning 24 hr prepartum. One pup (1-2 days old) was placed outside the nest at 0900 and 2100 hr on day 15 of gestation and then at 0300, 0500, and 0700 hr on day 16. After 0700 hr, tests continued at hourly intervals until the onset of parturition. Both nulliparous and primiparous-pregnant hamsters were tested as well as virgin and nonpregnant primiparious animals which had their last litter experience 2 mo earlier. Seventy-three percent of the pregnantnulliparous and 100% of the pregnant-primiparous animals

19 di~iplayed maternal behavior (retrieving and crouching) prepartum. Both groups became maternal at about the same time on the morning of day 16 of pregnancy. However, because of a difference in the timing of parturition, the mean interval between the onset of maternal care and parturition was significantly longer in the primiparous group (6.7 hr) than in the nulliparous group (2.5 hr). The non-pregnant groups continued to kill pups at each of the repeated tests. Since estradiol and progesterone levels decrease sharply within the 48 hr prior to the onset of maternal care (Fig. 1), the decline of either of these hormones or of both may be important for the increase in maternal responsiveness during the short interval near term. Exogenous steroids given during this interval might therefore be expected to affect the display of prepartum maternal behavior. Administering 1 or 10/~g estradiol- 17/3-, 0.1 mg progesterone, or a combination of both hormones on day 15 failed to reduce the percentage of animals responding or to affect the timing of the preparturn onset of maternal care. In the progesterone-treated groups, parturition was delayed thereby increasing the interval between the first appearance of maternal behavior and delivery to 8.5-9.5 hr. Although the acute onset of maternal care occurs on the day of parturition, it is still possible that daily exposure to pups during earlier stages of pregnancy might reveal an influence of gestation. Hamsters on days 1, 5, 9, 13 and 15 were presented with 3 newborns and these pups were replaced every 24 hr until the animals retrieved and sat with the pups in the nest or until the animals failed to respond maternally during 7 days of testing [5]. Compared with a large group of intact virgins, the group tested on the first day of gestation had significantly longer latencies (70% maternal after 96 hr) suggesting a possible inhibitory effect of early pregnancy. In the other direction, the first indication of an increased responsiveness to pups occurred in the day 13 group where 11/12 animals were maternal after 48 hr of exposure to young, that is, approximately 24 hr prepartum. The responses of animals first tested on day 15 (55% maternal on the first test) were not different from those on day 15 in the group initially tested on day 13. These data confirm the earlier studies [23,35] that even with daily pup stimulation, short-latency maternal care appears only very late in pregnancy. Maternal behavior is clearly a product of some events related to late gestation but since it begins before delivery, the process of parturition per se is not essential. In recent studies we have injected ovariectomized virgin hamsters with estradiol benzoate and progesterone for 14 days and began testing their maternal behavior 2 days later. This procedure was designed to simulate the steroid patterns of pregnancy (Siegel and Rosenblatt, unpublished data). The hormone-treated animals failed to exhibit maternal behavior and instead cannabalized as often as the oil-injected controls. A number of reasons could account for this failure and additional studies should examine hormone doses, timing of the injections, and the use of other hormones.

The Postpartum Period

The most striking feature of the early postpartum period, apart from the onset of maternal care, is the incidence of cannibalism among normal, untreated, otherwise highly maternal hamsters. In an extensive series of studies aimed at

20 characterizing this behavior and examining those factors which might affect it, Day and Galef [8] found that approximatley 80% of parturient hamsters cannibalized an average of 2 pups with the majority of the killing occurring within the first 72 hr postpartum and tapering off over the next 3 days. A number of factors that might, reasonably, be expected to affect cannibalism had no effect on the frequency of pup killing. These included the stress of daily handling of the mothers for 10 days postpartum, the appearance and weight of the pups, and age of the mother (females were mated 0, 4, or 8 weeks after the onset of puberty). Further, there were no significant correlations between mean number of pups cannibalized and either parity or litter size although there was a trend for pup destruction to be more frequent among females rearing larger litters. Culling litters to 4 pups on the day of birth reduced the incidence of cannibalism whereas maintaining initial litter size by replacing cannibalized pups with foster young of the same age increased both the frequency and duration of pup killing. Thus the extent of pup killing could be influenced but not its appearance during the first 5 days. Females continued to cannibalize only until day 5 of lactation demonstrating that the cessation of pup killing is a function of either changes in the developing young, internal changes in the mother beginning around day 5, or some combination of these two factors. To test whether developmental changes in the pups were responsible for the absence of killing after day 5, the litters of one group of females were replaced daily with newborn pups. This failed to extend cannibalism beyond day 5 suggesting that the change occurs in the females and is related to the time since parturition. A further test was carried out by adding 4 same-age foster pups to litters on days 0, 2, 5, and 9 of lactation. Increased cannibalism was observed only in those females given the additional pups on days 0 and 2. This again points to the importance of changes in the female during the early postpartum period which limit the period of cannibalism. Finally different groups of hamsters had their litters culled by 2 pups or increased by 2, 4, or 6 newborn foster pups on the day of parturition. The degree of cannibalism was almost directly proportional to the number of pups added and the foster pups were not destroyed any more frequently than the mothers' own pups. Day and Galef [8] concluded that "litter cannibalism appears to be a carefully organized and regulated aspect of maternal behavior in the golden hamster, which allows the parturient female to adjust the number of young which she must nurture." However, as mentioned above, the authors found no significant correlation between the different sizes of naturally occurring litters and number of pups cannibalized. It has also been suggested that the females may adjust their litters in response to environmental conditions (for example, food supply) although there is no supporting evidence at this time. In addition to displaying relatively high levels of cannibalism, the recently parturient female i.s highly aggressive towards males [42]. Lactating hamsters displayed the highest frequencies and shortest latencies for fighting, pouncing, and chasing when compared to cycling, pseudopregnant, and pregnant animals. Furthermore, animals tested during the first five days of lactation have significantly higher mean levels of these measures of aggressive behavior than do groups tested between days 15 to 20 of lactation. It is reasonable to believe that cannibalism and conspecific aggression share a common physiological mechanism since they occur at high levels during the same early

SIEGEL AND ROSENBLATT postpartum period. One likely causal agent is prolactin because of its early appearance and well-established role in lactation; serum prolactin levels during the lactation (Fig. 1) are higher than at any time during the estrous cycle except for a 1-3 hr peak (30 mg/ml) on the afternoon of proestrus [3]. Consequently, Wise and Pryor [43] treated postpartum hamsters with either ergocornine hydrogen maleate, an inhibitor of prolactin release, ergocornine plus exogenous prolactin, or vehicle injections. The animals were injected on days 4 and 7 and tested in a neutral area with males on day 7. The mothers had been ovariectomized (and hysterectomized) on day 4 to eliminate any possible effect of endogenous estrogen and progesterone on aggression. Litters remained with the mother to maintain high levels of suckling although the pups of ergocornine-treated animals received little milk and required cross-fostering; as a control, the vehicle-injected mothers also received foster pups. The results demonstrated that the control animals were clearly the most aggressive as measured by the percentage of each group responding aggressively to males and the frequency and latency to pounce, fight, chase, and roll. Aggression was somewhat lower in the ergocornine-treated group with prolactin replacement although the levels of aggression were relatively high whereas only one of the ergocornine-treated hamsters displayed minimal aggression. A second experiment by Wise and Pryor [43] showed that the administration of ergocornine had no effect when injected under conditions of presumably low endogenous prolactin levels. Long-term ovariectomized, nonlactating females treated with ergocornine displayed normal high levels of aggressive behavior in home cage tests with "intruder" males. Further evidence that high levels of prolactin may contribute to aggression has been shown using ovariectomized hamsters which received donor pituitaries transplanted to the kidney capsule [4]. Tests in neutral arenas with weight-matched males and females showed that the transplant group was significantly more aggressive than the ovariectomized, sham-transplant controls. Thus, an increase in prolactin during lactation or after pituitary transplantation appears to heighten aggression even in the absence of ovarian steroids. However, other factors seem to be involved in the display of aggressive behavior at other times in the reproductive cycle; for example, during the estrous cycle and on day 10 of pregnancy when aggressive behavior is high [42] and prolactin is low (Fig. 1). The ergocornine-induced reduction of prolactin release which eliminated almost all aggression towards males was accompanied by an increase in pup cannibalism and deficiencies in nest building and time spent in the nest [43]. About 42% of the ergocorning plus prolactin group and 70% of the ergocornine only group killed their own litters and replacements. In contrast, only 7% of the control mothers killed an entire litter. This lack of correlation between levels of aggressiveness and cannibalism was also reported in a group of virgin animals by Marques and Valenstein [15]. These data, the first to implicate a role for prolactin in maternal behavior, require further study. Although once daily determinations of prolactin during the periparturient period do not show a change, near constant levels of prolactin may have a greater effect following the decline of ovarian steroids which begins on day 14 of pregnancy and continues into lactation (Fig. 1). Studies employing prolaetin blockers, pituitary transplants, and the administration of prolactin to virgin animals should clarify the contribution of this hormone to the onset of maternal care.

MATERNAL BEHAVIOR IN HAMSTERS Another area of investigation during the e ~ l y postpartum period in the hamster pertains to the establishment of the mother-young bond which helps to ensure the survival of the young. One question that can be asked is: How much contact between mother and young is required, immediately postpartum for the mother to be able to sustain her maternal responsiveness after the young are removed? Hamsters were permitted either 1, 24, or 48 hr of pup contact postpartum prior to removal of their litters [36]. Test pups (1-2 days old) were then offered daily to independent groups of animals. Groups of animals allowed 1 hr of litter experience following parturition were maternal for 3 days (days 2, 3, and 4 of lactation) but cannibalized on the fifth and sixth days. Litter contact during the first 24 hr increased the interval during which the animals remained maternal by 1 day. However, groups with 48 hr of pup exposure were able to sustain their maternal behavior from day 4 to day 15 and only began to kill the test young on days 16 and 17. In another test of the strength of long term effects of the mother-young bond, primiparous hamsters exposed to their litters for the initial 36-48 hr postpartum were tested 3 or 6 weeks later with newborn pups [5]. Approximately one-third of these groups were immediately maternal upon reexposure and dally testing resulted in 100% of the 3 and 6 week groups showing maternal care after 72 and 48 hr respectively. These results are difficult to interpret. On the one hand, the 48 and 72 hr latencies are not much different from those of virgin animals exposed to pups for the first time (see next section). However, the proportion of animals responding immediately suggests that the prior experience of pregnancy, parturition, and the initial 1.5-2 days of litter contact may have increased the animals' sensitivity to pups 3 and 6 wk later. The importance of continuous contact with pups may lie in the maintenance of high levels of maternal responsiveness during lactation. The onset of maternal behavior at parturition may arise from prepartum physiological changes but these physiological conditions are no longer present during lactation particularly with respect to the relative levels of estradiol, progesterone, and prolactin (Fig. 1). The establishment of a mother-litter bond might be the mechanism providing for the maintenance of maternal care until weaning begins. We will return to this point in a later section. Daily 30 min observations of lactating hamsters show that the highest frequency of maternal behavior (sniffing, licking, nursing, and retrieving of the pups and nest building) occurs during the first week postpartum [7,40]. There is a significant decline in these types of behavior and a significant increase in nonmaternal behavior (including eating, drinking, moving about the cage, self-grooming, digging, stretching, and environmental sniffing) after the first week until three and one-half weeks. Rowell [33] reported that retrieving as well as nest building cease on day 22 and within the next week, the pups stop attempting to suckle and are occasionally attacked by their mother signaling the end of the gradual process of weaning. No differences have been found in the frequency of maternal or nonmaternal behavior in mothers undergoing their first or second lactation [40]. There are, however, several differences during the second lactation; as retrieving wanes, latency to pup retrieval increases dramatically 3 days later on day 18 in multiparous animals and retrieving stops completely 2 days later on day 24. The changing behavior of the mother appears to be synchronized with the developing needs and characteristics of

21 ho~!]itt~'. !Spending, more time in the nest, retrieving displaced pups, and initiating nursing bouts are common maternal activities in the early phase of lactation and they decline as the young become capable of greater mobility, seeking out the mother, and eating solid food. The maternal component of mother-litter synchrony has been studied by testing lactating females for their response to young of varying ages. Rowell [32] presented strange pups between 1-30 days of age to mothers at different stages of lactation. The mothers' behavior was divided into four categories which consisted of treating the pups as a member of her own litter, as a strange adult, as food, or with ambivalence, including both accepting and rejecting the pups during the same test. Mothers accepted pups between 7-14 days of age more frequently than during any other age-range, regardless of the age of the mothers' own litters. Time elapsed since parturition was also important: there were fewer rejections of pups of all ages as lactation progressed. Finally, there was a relationship between the age of the mother's current litter and the stimulus pups she responded to most strongly; females accepted those test pups that were closest to the age of their own litters. These findings led Rowell to study lactating animals kept with constant age litters to determine how unchanging pups of different ages affected the mothers' responsiveness. She maintained lactating hamsters with litters of 2-6, 6-10, 10-14, or 14-18 day old foster young and measured the time spent licking the pups after retrieval, the time spent out of the nest, and the duration of lactation [32]. Whereas the licking times of mothers with their own growing pups declined with advancing days since parturition and increasing age of pups, the licking times of mothers with foster litters were related to the age of the pups instead of the interval since delivery. Declines occurred, however in the time spent out of the nest and the duration of lactation as in the control mothers, suggesting that time elapsed since parturition was a more critical variable than the age of the pups being reared by the mothers. More recently, Swanson and Campbell [38] switched the litters of mothers that had been lactating for 3 and 12 days. Females foster rearing the younger litters nursed for 37 days postpartum (12+25 days), more than 10 days longer than Rowell [32] had reported. Females foster rearing the older pups nursed for 22 days postpartum (3+ 19 days) which was similar to control females nursing their own litters. The younger pups were therefore weaned at 28 days of age and the older pups at 31 days of age. These data show that in terms of nursing behavior the mother is responsive to the external stimuli originating from the litter and adjusts her behavior to their capabilities but endogenous maternal factors also play some role in determining the limits of this adjustment. RESPONSES OF NONPARTURIENTHAMSTERSTO PUPS Several investigators have exposed nonpregnant, nonparturient hamsters to pups and observed their responses. These experiments have been performed for a number of different reasons and have employed a variety of testing conditions. This section will summarize the findings of these studies beginning with the responses of adult females. As cited previously, Richards [23] placed 3 newborns directly into the sleeping nests of virgin females and found that all animals killed all of the test pups. In an earlier study,

22 Rowell [34] tested nulliparous, pregnant, and nonlactating but experienced females. The test pups, 3-11 days old, were placed either on the floor of the cage or in the nest in the adult's absence. The results were combined across reproductive conditions and they showed again that the most common response is cannibalism. Cannibalism occurred in each of the 20 tests in which pups were placed on the cage floor outside the nest whereas maternal behavior was shown in 3 of 13 tests in which pups were placed into the nest. Responses to pups, however, can be altered by prior exposure to them. In a study by Noirot and Richards [19], adults were initially exposed to a pup that was either 1,5, or 9 days old. Presentation of the 1 day old pup was accompanied by killing and eating of the pup by all of the females whereas the 9 day old pups elicited a few long-latency attacks but some maternal responses by all of the adults. Responses to 5 day old young in initial tests were intermediate between those to 1 and 9 day old young. In their second tests two days later, all of the females were exposed to 5 day old pups. Compared to control animals exposed to 5 day old young only once, the group originally exposed to the 9 day old pups attacked significantly less often and did not cannibalize at all. The behavior of the group exposed to 5 day old young on both tests showed little change whereas the animals previously presented with newborns displayed more nest building and carrying of pups, and spent less time eating but in the event of cannibalism, they had a shorter latency to the f'trst attack. In a more recent study, Marques and Valenstein [15] presented three or four 2-9 day old pups to intact females in a neutral test arena. The pups were scattered on the cage floor and the females were tested during the dark phase of the diurnal cycle. Approximately one-half of the females killed the pups whereas the remaining animals were observed cartying the pups but not necessarily retrieving the young to the nest. Further, five of the females that killed were ovariectomized and again killed upon re-testing two weeks later. The finding that almost one-half of the intact virgin females carried instead of killed pups is unusual compared to the majority of animals which are reported to cannibalize in other studies ([19, 23, 24]; see also [35,36]). The age of the test pup may be an important consideration. This will be discussed in the next section but it must be mentioned here that pups which are at least 6 days old are more often treated maternally (that is, licked, retrieved, and crouched over) than are younger pups [22]. Thus, the older pups within the 2-9 day range used in the study by Marques and Valenstein [15] may have contributed to the higher proportion of nonkillers. Most of the studies cited thus far have presented pups for either a single test period or for two tests separated by intervals ranging from 2 days to 2 weeks. The possibility that multiple tests over a short period of time might affect the degree of cannibalism has been investigated. Nulliparous animals were used as a control in the study mentioned earlier in which pregnant animals were presented with 1-2 day old pups [35]. Both the pregnant and virgin hamsters were tested an average of 6-8 times within 24 hr. Despite this frequent exposure to pups the majority of nonpregnant hamsters continued to kill the pups at each of these test periods. Sensitization, the induction of maternal behavior as an outcome of repeated or continuous exposure to test pups, was attempted in adult virgin female hamsters [39]. The animals were offered 1 or 2 pups between 6-12 days of age twice dally until they retrieved the pups and crouched over them

S I E G E L AND R O S E N B L A T F for two consecutive days or until they failed to respond during 10 days of testing. The mean latency to the onset of maternal behavior was 18 hr for 6 of 8 animals which killed pups on the initial test; two animals were excluded because one retrieved and crouched on the first test and one did not respond within 10 days. Four days of exposure to the exteroceptive cues of the pups which were kept in wire mesh boxes attached to the home cages failed to shorten subsequent latencies. The mean latency in this case was 33 hr which did not differ significantly from that in the first experiment (18 hr). Additionally, animals sensitized l l wk earlier showed no reduction in latency to become maternal upon re-sensitization. These data indicate that the female hamster is capable of altering her behavior as a result of multiple exposures to pups at short intervals lasting 2-3 days. However, as in the study by Marques and Valenstein [15], the age range of the test pups may have been responsible for the positive results. Therefore, in our study [37] on the sensitization of intact and ovariectomized naive hamsters we used 1-2 days old young which are more readily cannibalized, at least on first presentation. The animals were presented with 3 pups twice daily during the light phase at 1000 and 1500 hr. All ofthe 11 intact and 14 ovariectomized animals displayed maternal behavior (retrieving and crouching) and there were no differences between the groups in terms of the latencies to the onset of the behavior. Counting the first day of testing as day 1, the 25 animals had a mean latency of 1.8 days (43 hr) which is quite similar to that found by Swanson and Campbell [39] and by Buntin et al. [5] who tested virgin hamsters once daily with newborn pups. The importance of the sensitization capacity of the hamster will be discussed later. As shown in parturient animals, the virgin female, once sensitized, is capable of retaining her responsiveness to young in the absence of contuous pup exposure ([5]; Buntin, Jaffe, and Lisk, unpublished data), Following the initiation of retrieving and crouching, virgin females were permitted 12-36 hr of contact with the newborn foster pups. Resensitization latencies 3 weeks later were significantly shorter than those leading to the initial induction of maternal care. Two additional groups were presented with pups for 21 days; one group was given pups of advancing age each day while the other group was exposed to newborn pups for the 3 week period. After an additional 3 weeks, both groups were tested with young pups. Animals exposed to the young constant age pups were highly responsive and 90c7c displayed retrieving and crouching on the first day of testing while the group exposed to pups of advancing age who had undergone weaning of the young and a decline in maternal behavior were initially unresponsive and required 48--72 hr to show maternal behavior. The experience of weaning, an active process on the part of the mother, may have been retained over the 3 week interval without young, thereby reducing her responsiveness to the newborn test pups. It has been reported that male hamsters living with lactating females do not generally attack the litter [10]. Other studies have investigated the responses of the male hamster to pups in the absence of the mother. The f'mst of these found that 5 of 8 males sniffed and licked the ano-genital regions of the pups and then retrieved them to the nest although a lack of crouching was reported [34]. Marques and Valenstein [15] showed that all 14 of their males carried pups and engaged in nest building within 5 hr. Castration with or without 7 dally injections of 1 mg progesterone failed to significantly alter the males' responses. In contrast to these results are the

MATERNAL BEHAVIOR IN HAMSTERS findings of Swanson and Campbell [39]. Their males re, sponded maternally with a mean latency of 72 hr which was significantly longer than that of females (18-33 hr). There was a greater incidence of incomplete retrievals in the males and they showed a type of crouching which was qualitatively different from that of females; males curl their bodies around the pups and never adopt the lactating posture in which females straddle the litter providing easy access to their nipples. Differences in latencies in the males' responses in these two studies may be related to differences in testing conditions (Marques and Valenstein used neutral cages whereas Swanson and Campbell presented pups in the animals' home cages). Finally, the response of juvenile hamsters will be briefly discussed. The earliest display of maternal behavior (licking and mouthing of the 1-8 day old pups) was observed at 15 days [34]. There were no differences between male and female juveniles and all 10 litters showed some maternal responding by 19 days. Litters living with their mothers began cannibalizing pups at a mean age of 37 days while the litters without their mothers continued behaving maternally past 50 days. In summary, females, males, and juveniles of both sexes are capable of exhibiting maternal care and cannibalism. The naive female is typically highly cannibalistic, but she can be sensitized to pups ranging in age from 1-12 days, and is capable of retaining her maternal responsiveness for at least 3 weeks in the absence of further pup exposure. The responses of males appear less efficient and less cannibalistic than those of females across different testing conditions. Studies of juveniles indicate that the animals are initially maternal and later begin to cannibalize but the age at which this occurs is affected by litter conditions (for example, the presence or absence of the mother).

NEURAL BASISOF MATERNALBEHAVIOR Only a few studies have investigated the neural basis of maternal responsiveness in virgin and parturient animals. Neonatal olfactory bulbectomy resulted in one-third of the animals killing their litters in adulthood [13]. In addition, the normally high levels of aggressive behavior during pregnancy and lactation were eliminated in the early bulbectomized animals demonstrating again the lack of correlation between conspecific aggression and cannibaslim. More recently, the effects of the olfactory system on maternal behavior has been re-examined [ 14]. Bilateral bulbectomy in adulthood, including destruction of the anterior olfactory nucleus, reduced both killing and carrying pups among virgin female hamsters whereas bulbectomy without the additional damage resulted in pup destruction among animals which had carried pups in pre-operative tests. The results, however, were not due to the loss of olfaction p e r s e because zinc sulfate treatment, a procedure used to produce peripheral anosmia, did not alter the animals' pre-operative killing or carrying behavior. Carrying pups was observed following vomeronasal cuts in animals which killed pups during a pre-treatment test and this effect was potentiated by zinc sulfate. The effects of hypothalamic knife cuts on maternal care has been studied in virgin and parturient animals [16]. Anterior cuts lateral to the medial preoptic area-medial anterior hypothalamus and posterior cuts lateral to the medial anterior hypothalamic-ventromedial nucleus were made in vir-

23 gi~females f o U ~ apre-test to determine their initial response to pups. The animals were then tested during the dark phase for 5 rnin in neutral test cages with one pup between 2-4 days of age. The anterior cuts resulted in pup destruction and decreased nest building regardless of whether the animals killed or carried pups pre-operatively. All parturient animals (9/9) with anterior cuts killed their litters over the first 5 days postpartum although one-half of these animals did retrieve pups in home cage tests during the same period. The results of the posterior cuts were less consistent in the naive group. One-half (5/10) of the animals that killed preoperatively continued to kill and 3/10 retrieved the test pup while 2/7 of the females that retrieved pups prior to the knife cuts continued to do so and 3/7 destroyed the pups. However, parturient animals with posterior cuts did not kill pups and in fact, by day 5 they had litters that were larger than those of controls. METHODOLOGICALCONSIDERATIONS In reviewing the studies thus far, we have included a number of methodological details. Our present understanding of the regulation of maternal behavior in the hamster is stiff quite limited and the design of future studies requires an appreciation of the variety of testing conditions which have been employed. Table 1 summarizes those experimental procedures which have most heavily influenced the outcome of maternal behavior studies in this species. One of the crucial factors influencing the responsiveness of lactating and virgin hamsters is the age of the stimulus pup. Although other factors are involved, the lactating hamster presented with pups of different ages is most maternal towards 7-14 day old young [32]. A detailed analysis of the effect of the age of the pup in naive females showed clearly that pups between 6-10 days of age elicited the most maternal responsiveness [22]. Eighteen groups of eight females were each tested once with three pups which were 1-18 days of age. The youngest pups (1-6 days) were attacked and killed and the oldest pups (11-18 days) were treated as adult intruders and elicited the most territorial marking by the females. Presentation of pups in the middle age range was accompanied by the highest levels of carrying, nest building, and crouching. These data demonstrate that the age range of the stimulus young used to test adult animals is an important consideration. The effect of presenting females with more than one pup at each test is best illustrated by one study on lactating hamsters [8] and one on pregnant animals [23]. First, there was a trend for animals delivering larger litters to cannibalize more of their young. Second, adding foster pups to the litters proportionally increased the amount of cannibalism. Third, the response to the first of several pups can be very different from the response to subsequently encountered pups. Pregnant animals near term typically killed the first pup but retrieved and crouched over the second or third pup they contacted. Related to the procedure of using more than one pup per test is the use of longer observation periods and repeated testing. Most studies employ short test periods because the hamster often retrieves or cannibalizes within 1-2 min. However, valuable information can be obtained by extending the observation sessions. For example, 9 of 14 males carried pups within the initial 10 min while the remaining 5 were seen carrying only during spot checks over the next 5 hr [15]. Nest building is sometimes displayed after the animal

24

SIEGEL AND ROSENBLATT TABLE 1 EFFECTS OF DIFFERENT TESTING PROCEDURES ON MATERNAL RESPONSIVENESS IN HAMSTERS

Procedure

Effect

Reference

Age of test pup

>6 days treated more maternally <6 days cannibalized more frequently

19,22,32

Number of test pups

First pup contacted may be treated differently than next pups

8,23

Length of test interval

Carrying, nest building, crouching observed after initial test period

15

Number of test periods

Sensitization

5,37,39

Pup placement

Pups more frequently accepted if placed into nest

33,34

Test cage

Neutral test arena may reduce cannibalism

15,34,39

has retrieved the pup but it is not uncommon for nest building to occur after the animal has ~ [15,22]. Recent studies demcmatrate that the majon'ty of hamsters change from canm'helism to maternal responsiveness after multiple tests over relatively short intervals ranging from several hours to 2-3 days [5, 37, 39]. Thus, differences in latencies to become maternal may be used to determine the effectiveness of a variety of experimental treatments (for example, hormone injections or pharmacological manipulations). There is evidence that placement of the pup directly into the nest instead of on the cage floor may result in more frequent ae.c~tance of the y o u ~ [34]. Also, observations of parturition have sullBeated that pups bern outside of the nest are abandoned more often than those bern in the nest [33]. Therefore, the results of several studies already discussed [19, 22, 23] may have been inflt~nced b y this procedure. Most studies have used the animals' home cages as the test cages. However, in one case, female and male hamsters were tramferred to neutral testing arenas and then presented with pups 1 hr later [lb']. The remtlts suggest that neutral cages may reduce the incidence of cnunibalism (for example, [39]) and this may he related to the high degree of territoriality that exists in this species [34]. In addition to the factors listed in Table 1, there are a number of other variables which may affect experimental results and conclusions. Daily handling from days 1-10 postpartum did not reduce cannibalism but daily handling as opposed to forceps-handling started at weaning led to greater reproductive success as measured by the numbers of abortions, live litters, live young at birth, and young raised to weaning [41]. The effects of group housing on reproductive success and maternal care l a v e recently ~ investigated [9]. Groups of 1, 2, 4, or 6 females lived with 2 males for 60 days in cages measuring 11×60×30 cm. ~ there were no differences in the mean number o f ~ e s or litters resorbed, there was a ~ l n i f l c a a t ~

of ~

gronp size on the

mean ~ of litters destroyed. Only 17% of the litters among ~ female groups were ~ while 100% of the litters were destroyed in those groups consisting of 6 females.

Another factor which would he valuable to examine is when testing should be done ~ the ~ - d a t k cycle. In most studies, animals have been tested ~ t h e dafkphase because this is the time of their greatest activity. However, the highest levels of maternal care are e~sexved at parturition which commonly occurs in the m i d ~ ofthelight phase. This point is related to the natural ~ under which maternal behavior first appem,s. The hamster is e xp~.ed to 6-10 newborn Imps which she encounters one at a time m her nest in the home cage. Experiments desillmK! to test the effectiveness of each of these variables directly are currently underway in our laboratory. THEORETICAL FRAMEWORK

This section will attempt to oqlanize the available evidance on maternal behavior in the ~ into a t h e o t ~ c a l framework. This framework proposes tlmt there are two phases in the regulation of m a m m l behavior in the hamster and is similar to the one that has been ~ for the rat [27,28]. The two phases ~ an onset coaqmnent that is based on internal chaages in the mother which~ ~ turn and a maintenance ~ which is ~ upon both endogenous factors and external, litter~einted factors. We suggest further that these two ~ l ~ l l u ~ ~ ~ a transition period which ~ at pQrtta'ilioa aRdit is d t a ~ this transition period that a ~ in the ~ o f ~ care

occurs.

The onset of maternal behavior, which, under normal conditions appears to occur ~ m m u e o u s l y at parturition, actually begins p ~ m [23,3~. The c ~ from cannibalism in the naive and even ~ ~ t o responsiveness in the very late ~ ~ i s ~ w dent of Imp ~ and the eveaN ~ with deft'very of the lttm'. ~ t h e l e is I t o e ~ k fori are involved (see [3:~q), ,t~,~psrlieular ~ . .). . . . ~ the chanse in the fenmte s behavior is ~ e l y ~ tmkaown closely related to rite ~ prepartum) s h o n l d b e ~

is, the 24-48 •

Because it is emtllmly that ~ ~ ~ conditions leading to the onset of matemat cere e ~ f l n ~ - t h m n g h -

MATERNAL BEHAVIOR IN HAMSTERS

25

out the lactation period, the maintenance of maternal responsiveness may be dependent upon stimulation the female receives from her litter. The importance of the fu'st 24-48 hr of postpartum litter contact on later maternal behavior [36] is evidence that stimulation from the pups is necessary for maintaining the female's responsiveness even in the absence of continuous litter exposure. Exposure to litters for 1 or 24 hr postpartum was not sufficient to establish the maintenance phase whereas the initial 48 hr of pup stimulation enabled the females to make the transition and their responsiveness persisted. Although the removal of litters in the studies by Siegel and Greenwald [36] and Buntin et al. [5] led invariably to the resumption of estrous cyclicity within several days [11], maternal behavior was retained; it is clear that the physiological conditions associated with cyclicity (for example, the lack of chronically high levels of prolactin found during lactation) do not affect the retention or subsequent display of maternal behavior. In addition, as cited earlier, ovariectomy during the first week of lactation does not affect the ongoing maternal behavior [43] suggesting that the ovarian steroids are not essential for the maintenance o f the behavior. Thus, these two situations, the change from diestrus to cyclicity and the absence of ovarian hormones, demonstrate that the maintenance phase of maternal care continues under conditions that are quite different from those associated with the onset phase. Sensitization provides additional evidence for the effectiveness o f pup stimulation. During sensitization, latencies are prolonged but prepartum hormonal conditions may act

tlpOn this capacity o f the hamster to produce immediate maternal behavior at parturition and even earlier. Although parturition may not be essential for the later expression of maternal care, it may still play a role in focusing the attention of the endogenously primed female of the salient characteristics of the young. The postpartum hamster still appears to be dependent on some, as yet unknown, internal factor which paced her behavior toward her young. Her responses to foster young [32] and the basis for her " n o r m a l " cannibalism are related to the number of days which have elapsed since parturition. Although pharmacological reduction in prolactin levels has been associated with higher levels of cannibalism [43], the role of prolactin requires further experimentation. The data indicate that maternal behavior can be elicited from either internal pregnancy-related changes or external pup-related stimuli. We suggest that both types of stimulation play important roles in the normal maternal behavior cycle but as successive phases in the cycle. Some of the major questions remaining include the determination of the near term event or series o f events leading to the replacement of cannibalism as the predominant response with maternal behavior and the exact relationship which begins at birth between this mechanism and that of pup stimulation. In addition, the processes related to the pup killing commonly observed in the postpartum hamster need to be explained and this may provide some insight into why some animals destroy larger parts o f their litters and why the naive animal is so highly cannibalistic.

REFERENCES 1. Baranczuk, R. and G. S. Greenwald. Plasma levels ofoestrogen and progesterone in pregnant and lactating hamsters. J. Endocr. 63: 125-135, 1974. 2. Bast, J. D. and G. S. Greenwald. Daily concentrations of gonadotropins and prolactin in the serum of pregnant or lactating hamsters. J. Endocr. 63: 52%532, 1974. 3. Bast, J. D. and G. S. Greenwald. Serum profiles of folliclestimulating hormone, luteinizing hormone and prolactin during the estrous cycle of the hamster. Endocrinology 94: 1295-1299, 1974. 4. Buntin, J. D., C. Catanzaro and R. D. Lisk. Elevation of prolactin levels by pituitary transplantation: Effects on intraspecific aggression in female golden hamsters (Mesocricetus auratus). Presented at Animal Behavior Society, New Orleans, 1979. 5. Buntin, J. D., S. Jaffe and R. D. Lisk. Physiological and experiential influences on pup-induced maternal behavior in female hamsters. Presented at Eastern Conference on Reproductive Behavior, New Orleans, 1979. 6. Ciaccio, L. A. and R: D. Lisk. Hormonal control of cyclic estrus in the female hamster. Am. J. Physiol. 221: 936-942, 1971. 7. Daly, M. The maternal behaviour cycle in golden hamsters. Z. Tierpsychol. 31: 289-299, 1972. 8. Day, C. S. D. and B. G. Galef. Pup cannibalism: One aspect of maternal behavior in golden hamsters. J. comp. physiol. Psychol. 91: 1179-1189, 1977. 9. Diamond, M. and M. Mast. Crowding, reproduction, and maternal behavior in the golden hamster. Behav. Biol. 23: 477--486, 1978. 10. Dieterlen, Von F. Das verhalten des syrischen Goldhamsters (Mesocricetus auratus Waterhouse). Z. Tierpsychol. 16: 47-103, 1959. 11. Oreenwald, G. S. Histoiogic transformation ot the ovary of the lactating hamster. Endocrinology 77: 641-650, 1965. 12. Kislak, J. W. and F. A. Beach. Inhibition of aggressiveness by ovarian hormones. Endocrinology 56: 684-692, 1955.

13. Leonard, C. Effects of neonatal (Day 10) olfactory bulb lesions on social behavior of female golden hamsters (Mesocricetus auratus). J. comp. physiol. Psychol. 80:. 208-215, 1972. 14. Marques, D. M. and E. S. Valenstein. Separate olfactory and neural systems mediate maternal behavior, cannibalism, and cricket killing the female hamster. Paper presented at Society for Neuroscience, 1976. 15. Marques, D. M. and E. S. Valenstein. Another hamster paradox: More males carry pups and fewer kill and cannibalize young than do females. J. comp. physiol. Psychol. 90: 653-657, 1976. 16. Marques, D. M., C. W. Malsbury and J. Daood. Hypotbalamic knife cuts dissociate maternal behaviors, sexual receptivity, and estrous cyclicity in female hamsters. Physiol. Behav. 23: 347355, 1979. 17. Moltz, H. The ontogeny of maternal behavior in some selected mammalian species. In: Ontogeny of Vertebrate Behavior, edited by H. Moltz. New York: Academic Press, 1972, pp. 263-313. 18. Noirot, E. The onset of maternal behavior in rats, hamsters, and mice: A selective review. In: Advances in the Study of Behavior, edited by D. S. Lehrman, R. A. Hinde and E. Shaw, Vol. 4. New York: Academic Press, 1972, pp. 107-145. 19. Noirot, E. and M. P. M. Richards. Maternal behavior in virgin female golden hamsters: Changes consequent upon initial contact with pups. Anim. Behav. 14: 7-10, 1966. 20. Payne, A. P. and H. H. Swanson. Hormonal control of aggressive dominance in the female golden hamster. Physiol. Behav. 6: 355-357, 1971. 21. Richards, M. P. M.Aspects of maternal behaviour in thegolden hamster. Doctoral Dissertation, Cambridge University, 1965. 22. Richards, M. P. M. Maternal behaviour in virgin female golden hamsters (Mesocricetus auratus Waterhouse): The role of the age of the test pup. Anim. Behav. 14: 303-309, 1966.

26

23. Richards, M. P. M. Maternal behaviour in the golden hamster: Responsiveness to young in virgin, pregnant, and lactating females. Anita. Behav. 14: 310-313, 1966. 24. Richards, M. P. M. Activity measured by running wheels and observation during the oestrous cycle, pregnancy, and pseudopregnancy in the golden hamster. Anita. Behav. 14: 450-458, 1966. 25. Richards, M. P. M. Maternal behaviour in rodents and lagomorphs. In: Advances in Reproductive Physiology, edited by A. McClaren, Vol. 2. London: Logos Press, 1967, pp. 53110. 26. Richards, M. P. M. Effects of oestrogen and progesterone on nest building in the golden hamster. Anita. Behav. 17: 356-361, 1969. 27. Rosenblatt, J. S. Views on the onset and maintenance of maternal behavior in the rat. In: Development and Evolution of Behavior: Essays in Memory of T. C. Schneirla, edited by L. R. Aronson, E. Tohaeh, D. S. Lehrman and J. S. Rosenblatt. San Francisco: Freeman, 1970, pp. 489-515. 28. Rosenblatt, J. S. Prepartum and postpartum regulation of maternal behaviour in the rat. Ciba Foundation Symposium, No. 33. Amsterdam: Assoc. Scientific Publ., 1975. 29. Rosenblatt, J. S. and D. S. Lehrman. Maternal behavior in the laboratory rat. In: MaternalBehavior in Mammals, edited by H. L. Rbeingold. New York: Wiley, 1963, pp. 8-57. 30. Rosenblatt, J. S. and H. I. Siegel. Maternal behavior in the rat. In: Maternal Influences and Early Behavior, edited by R. W. Bell and W. P. Smotherman. New York: Spectrum, 1980, in press. 31. Rosenblatt, J. S., H. 1. Siegel and A. D. Mayer. Progress in the study of maternal behavior in the rat: Hormonal, nonhormonal, sensory, and developmental aspects. In: Advances in the Stud), of Behavior, edited by J. S. Rosenblatt, R. A. Hinde, C. Beer and M.-C. Busnel, Vol. 10. New York: Academic Press, 1979, pp. 225-311. 32. Rowell, T. E. On the retrieving of young and other behaviour in lactating golden hamsters. Proc. zool. Soc. Lond. 135: 264-282, 1960.

SIEGEL AND ROSENBLATT 33. Rowell, T. E. The family group in golden hamsters: Its formation and break-up. Behaviour 17: 81-93, 1961. 34. Rowell, T. E. Maternal behaviour in non-maternal golden hamsters (Mesocricetus auratus). Anita. Behav. 9:11-15. 1961. 35. Siegel, H. I. and G. S. Greenwald. Prepartum onset of maternal behavior in hamsters and the effects of estrogen and progesterone. Hormones Behav. 6: 237-245, 1975. 36. Siegel, H. I. and G. S. Greenwald. Effects of mother-litter separation on later maternal responsiveness in the hamster. Physiol. Behav. 21: 147-149, 1978. 37. Siegel, H. I. and J. S. Rosenblatt. Short-latency induction of maternal behavior in nulliparous hamsters. Presented at Eostern Conference on Reproductive Behavior. Madison, 1978. 38. Swanson, L. J. and C. S. Campbell. Weaning behavior in the female hamster. Presented at Animal Behavior Society Meetings, Seattle, 1978. 39. Swanson, L. J. and C. S. Campbell. Induction of maternal behavior in nulliparous golden hamsters (Mesocricetus aratus). Behav. Neural Biol. 26: 364--371, 1979. 40. Swanson, L, J. and C. S. Campbell. Maternal behavior in the primiparous and multiparous hamster (Mesocricteus auratus). Z. Tierpsychol. 50: 96-104, 1979. 41. Yaron, E., I. Chovers and J. T. Groen. Influence of handling on the reproductive behavior of the Syrian hamster in captivity. J: Psychosom. Res. 7: 69--82, 1963. 42. Wise, D. A. Aggression in the female golden hamster: Effects of reproductive state and social isolation. Hormones Behav. 5: 235--250, 1974. 43. Wise, D. A. and T. L. Pryor. Effects of ergocornine and prolactin on aggression in the postpartum golden hamster. Hormones Behav. 8: 30-39, 1977. 44. Zarrow, M. X., R. Gandelman and V. H. Denenberg. Prolactin: Is it an essential hormone for maternal behavior in mammals? Hormones Behav. 2: 343--354, 1971.