A comparison of taste reactivity changes induced by ventromedial hypothalamic lesions and stria terminalis transections

Physiology & Behavior,

Vol. 44, pp.

699-708.

0031-9384/88 $3.00 + .OO

Copyright B Pergamon Press plc, 1988.Printed in the U.S.A.

A Comparison of Taste Reactivity Changes Induced by Ventromedial Hypothalamic Lesions and Stria Terminalis Transections RICHARD Department

M. BLACK

of Psychology,

McMaster

AND

P. WEINGARTEN’

University, Hamilton,

Received BLACK, R. M. AND H. P. WEINGARTEN.

HARVEY

Ontario, Canada,

LB.5 4KI

11 May 1988

A comparison

of taste reactivity

changes induced by ventromedial

hypotha-

PHYSIOL BEHAV 44(6)69%708, 1988.-A hyperreactivity to the sensory qualities of a food, i.e., finickiness, is a defining feature of the ventromedial hypothalamic (VMH) lesion syndrome. The precise anatomical locus mediating this disturbance has not been determined. This study examines the hypothesis that interruption of amygdalo-hypothalamic connections (either ascending or descending) via the stria terminalis (ST) is involved in VMH lesion-induced finickiness. Taste reactivity was assessed in animals with VMH lesions, ST knife cuts, combined VMH/ST damage, and controls. In sham feeding tests of taste reactivity, ST and VMH rats were equally hyperreactive compared to controls. Rats with combined VMH and ST damage, however, were more reactive than both these groups. None of the brain lesions resulted in an overreactivity to quinine adulteration of the diet. In contrast to sham feeding, ST rats were not hyperphagic when feeding normally, although VMH rats were. In fact, ST damage attenuated VMH-induced hyperphagia and weight gain. We conclude that the taste reactivity changes induced by VMH lesions and ST transections are independent and additive indicating that VMH finickiness does not involve disruption of amygdalohypothalamic connections. Nonetheless, disruption of the ST produces a dramatic change in taste reactivity and the properties and origins of this disturbance are discussed.

lamic lesions and stria terminalis

transections.

Ventromedial hypothalamus Amygdala Forebrain taste pathways Sham feeding

Stria terminalis

Palatability

Taste reactivity

They conclude that damage in the lateral-posterior portion of the VMH produces tinickiness but that more medial damage produces hyperphagia without changes in taste reactivity [although this interpretation has been criticized (29,36)]. The idea that ablation of a system involving more than just the VMH produces finickiness is supported by the observations that taste reactivity changes can also be produced by knife cuts or lesions of other hypothalamic nuclei. For example, parasagittal knife cuts lateral to the VMH, or coronal cuts posterior to the VMH, produce finickiness even though these cuts leave cell bodies in the VMH relatively intact (1, 35,36). PVN lesions, which do not encroach upon the VMH, but which may interrupt the same fiber systems affected by the hypothalamic knife cuts, also render rats finicky (1,41). The specific hypothesis examined in this study is that destruction of connections between the amygdala and hypothalamus is responsible for VMH lesion-induced changes in taste reactivity. Several observations support this hypothesis. First, the classic VMH lesion which produces the VMH syndrome destroys both of the major pathways linking the amygdala with the VMH-the ventroamygdalofugal pathway and the stria terminalis (ST) (7,9, 13,23). Second, damage to

ONE of the defining behavioral characteristics of the ventromedial hypothalamic (VMH) lesion syndrome is an overreactivity to the sensory properties of food [see (29,37) for reviews]. This symptom, termed “fmickiness” (38), profoundly influences the degrees of hyperphagia and weight gain in VMH lesion rats. For example, VMH rats display little or no hyperphagia and weight gain when maintained on unpalatable diets (10,ll). In contrast, hyperphagia and obesity are marked when VMH rats are maintained on palatable diets (3,4,5,21, 38). Although these taste reactivity changes are ubiquitous concomitants of VMH lesions, the exact anatomical loci mediating this effect is not identified. The typical lesion used to produce the VMH syndrome involves a large area of destruction in the basomedial hypothalamus. The finickiness of the VMH rat is often assumed to result from destruction of those cell bodies in the VMH which mediate the hyperphagia effect [e.g., (3,29)]. However, several investigations suggest that taste reactivity changes may result from damage to other cell bodies or to fibers passing through, or terminating in, the VMH. For example, GratT and Stellar (15) suggest that hyperphagia and finickiness result from destruction of different anatomical loci.

‘Requests for reprints should be addressed to Dr. H. P. Weingarten.

699

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BLACK AND WEINGARTEN

the amygdala produces a finicky-like pattern of food intake. Rats sustaining arnygdaloid lesions are not hyperphagic under usual maintenance conditions but overconsume a sweet 25% sucrose solution in a two bottle test (30). Similarly, damage to the medial amygdala, which is connected to the VMH via the ST (7, 22, 32), results in an overreactivity to saccharin solutions without accompanying overeating of less palatable foods (33). Third, the amygdala has already been demonstrated to influence aspects of feeding behavior through a neural circuit involving the ST and hypothalamus. Stimulation of the amygdalopyriform transition zone suppresses food intake in deprived rats and this effect is blocked by bilateral ST lesions (44). Box and Mogenson (2), based on their examination of the effects of amygdaloid lesions on ingestive behavior, suggested that the amygdala modulates hypothalamic activity via the ST. Finally, the view that amygdalo-hypothalamic connections are involved in VMHinduced finickiness is consistent with the traditional role ascribed to the amygdala, which is affective and sensory control of regulated and motivated behavior (12). G E N E R A L METHOD

Subjects Subjects were male Long-Evans hooded rats bred in the McMaster Psychology Department colony from stock originating from Blue Spruce Farms (Altmont, NY). They were housed individually in a room maintained at 21°C and on a 14:10 light:dark cycle. Water was available ad lib and food was provided according to the experimental protocol.

Surgery For both gastric and stereotaxic surgeries, rats were anesthetized with sodium pentobarbital (Somnotol) injected intraperitoneally (IP) at a loading dose of 45 mg/kg. Atropine sulphate (0.2 ml of 0.6% solution, IP) was administered to reduce salivary and mucous secretions during surgery. A chronically indwelling gastric cannula was implanted into each rat (42). Briefly, a midline laparotomy was made and the stomach exprsed. Two concentric purse string sutures were sewn into the anterior rumen of the stomach and an incision was made in the stomach wall encircled by the sutures. One end of a stainless steel cannula (8.5 mm o.d. × 7.9 mm i.d. × 11 mm long) was secured into the stomach. The cannula was exteriorized through a stab wound in the left abdominal wall and skin. The cannula was kept closed by a set screw threaded into the cannula shaft. Fourteen to twenty days of recovery were allowed after gastric surgery, during which time rats were maintained ad lib on Purina Rat Chow pellets. Following this, each rat underwent stereotaxic surgery. Rats sustained: 1) bilateral electrolytic lesions of the VMH with sham ST knife cuts (VMH group); 2) bilateral ST knife cuts with sham VMH lesions (ST group); 3) both VMH lesions and ST knife cuts (VMH/ST group); or 4) sham VMH lesions and sham ST

knife cuts (control). Subjects were assigned to the four experimental groups so that mean group weights and variances at surgery would be approximately equal. To produce VMH lesions, electrodes were lowered to: 2. l mm posterior to bregma, 0.6 mm lateral to the midline and 9.5 mm below the skull surface (with the incisor bar 3.0 mm below the horizontal). Electrodes were made of No. 00 stainless steel insect pins coated with epoxylite except for 0.4 mm at the tip. Lesions were produced by passing a 1.0 mA anodal current between the electrode and a tail cathode for 18 sec. For sham lesions, electrodes were lowered to the same coordinates but no current was passed. Knife cuts were produced using a spring-loaded brain knife (18). The knife was a 30 ga tungsten wire which fed through a 23 ga guide tube. The knife was positioned (with the incisor bar 3.0 mm below the horizontal) to 1.3 mm posterior to bregma, 4.7 rnm lateral to the midline and 5.2 mm below the skull surface. The tungsten knife was extended 3 mm in a caudal-medial direction, 45° to the midline, and the spring-loaded catch was released allowing the knife to travel 4.0 mm vertically. The wire was retracted and the knife removed from the brain. For sham knife cuts, the knife was lowered to the same coordinates and the trigger released but the tungsten wire was not extended. All subjects were deprived of food for 24 hr following stereotaxic surgery.

Test Cages and Sham Feeding Procedure' Animals were tested in individual Plexiglas cages, 10× 10×20.5 cm with a 1.5×20.5 cm slot in the center of the floor. The cage was mounted on 19.5 cm high stilts. A graduated cylinder with a drinking spout containing the test solution was attached to the front of each cage allowing the spout to protrude into the cage through a 2.5 cm circular hole in the front wall. To prepare a rat for testing, it was taken from its home cage and weighed. The set screw was removed and the stomach cleaned with lukewarm tap water applied through the cannula. A 19.1 mm long stainless steel collection tube attached to a 15 cm long length of Tygon tubing was threaded into the cannula. When the subject was placed in the test cage, the tube hung freely through the slot in the floor and ingested material drained out of the stomach, down the collection tube, and into a catch pan under the cage. The graduated cylinder containing the test solution was attached to the front of the cage and the initial volume recorded. Rats sham fed for 30 min; intakes were recorded every 5 min. At the end of the test, the rat was taken from the test cage, its drainage tube was removed, the set screw replaced, and it was returned to the home cage where it immediately received its daily food ration (Purina Rat Chow pellets) sufficient to maintain the required deprivation condition.

Sham Feed Training and Solutions For Experiments 1, 2, and 3, all rats were maintained at 95% of their weight prior to stereotaxic surgery, allowing 1 g

FACING PAGE FIG. I. Brain slices indicating a successful ST knife cut. The upper photograph depicts a coronal cut at approximately A.5340 g in the Konig and Klippel (19) atlas. The middle and lower plates are more caudal. The middle panel shows the knife cut passing directly through the ST. Abbreviations: CA3, CA3 of the hippocampus; CP, caudate putamen; Fi, fimbria; IC, internal capsule; ST, stria terminalis; VL, ventrolateral thalamus.

VMH, ST, AND TASTE REACTIVITY

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per day for growth. This pair-weighing procedure ensured that any behavioral differences observed were not secondary to body weight changes induced by the brain manipulations. Rats were reduced to this weight over a one week period. Rats were trained to sham feed reliably using an 18% sucrose solution. Any rat that failed to feed reliably by the end of training was not tested further. Sucrose solutions were prepared on a weight/volume basis, at least 24 hr in advance and presented at room temperature. Rats were tested twice at each sucrose concentration.

Histology At the completion of testing, rats were sacrificed using 1.0 ml of 50% chloral hydrate injected IP and were perfused intracardially with 0.9% saline followed by 10% buffered formalin. Each brain was removed, stored in 10% buffered formalin and sectioned at 40/zm in the coronal plane. Every second section through the lesion or knife cut was mounted and subsequently stained with luxol fast blue and cresyl violet (20). Subjects were assigned to groups based upon the location and extent of tissue damage, assessed by a rater blind to the experimental results. E X P E R I M E N T 1: S H A M F E E D I N G SWEET SUCROSE SOLUTIONS This study assesses the effects of VMH lesions, ST transections, and the combined manipulation, on responsivity to hedonically positive sweet solutions. Sham feeding is used since finickiness is a disturbance of taste reactivity and sham feeding, because it eliminates (or greatly minimizes) postingestional effects of food, provides an index of the degree to which intake is influenced by taste properties of food

(43). Also, sham feeding has been used successfully to explore taste reactivity changes in the VMH syndrome (6, 39, 41). If the taste hyperreactivity of VMH rats results from interruption of amygdaloid connections with this area via the ST, then rats with complete ST transections remote from the VMH should be as overreactive as VMH lesion rats. Furthermore, rats with combined VMH lesions and ST cuts should be no more reactive than rats with either VMH or ST damage alone. METHOD Thirty subjects (mean weight - 1 SEM at stereotaxic surgery was 443_+5 g) were assigned to the VMH (n=7); ST (n=8); VMH/ST (n=9); or control (n=6) groups. After initial sham feed training rats, rats were tested on 6, 12, 18, and 24% of sucrose, presented in a random order, one solution per test day. RESULTS

Histology The criterion for inclusion into the VMH group has been described elsewhere (39) and, briefly, required bilateral destruction o f at least 80% of the classically defined VMH. Typically, the lesions began in the anterior hypothalamus, destroyed the entire ventromedial nucleus, and terminated just anterior to the premammillary bodies. The damage extended laterally from the third ventricle to the fornix and dorsally from the base of the brain to the ventral aspect of the dorsomedial hypothalamic nucleus. Three of the seven rats with VMH lesions sustained this criterion damage and comprised the VMH group.

VMH, ST, AND TASTE REACTIVITY

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FIG. 3. Thirty min intakes (in ml) of the four groups of a 30% sucrose solution adulterated with increasing concentrations of quinine indicated.

To be included into the ST group, rats had to have complete bilateral transections of the ST. The stria terminalis was cut at its most dorsal excursion as it coursed along with the f'tmbria. At this location, the stria terminalis is a discrete fiber bundle and, severing it here interrupts all four of its subsequent component parts (8). A typical successful cut is shown in Fig. 1. The cuts extended in a medial-caudal direction from the candate putamen through the globus palladus to the anterior portion of the lateral posterior and posterior thalamic nuclei. Typically the fimbria and CA3 layer of the hippocampus were also damaged. Seven of 8 rats met this criterion. Five of nine rats sustained criterion damage to both the VMH and the ST and constituted the VMH/ST group. The six sham operated rats served as controls.

Body Weight and Food Intake The food restriction regimen employed was successful in maintaining equivalent body weights among the four groups. Statistical analyses indicated that body weights of the groups did not differ at either the initiation, F(3,17)= 1.89, p >0.05, or termination, F(3,17) = 1.94, p >0.05, of sham feeding tests. Figure 2 shows the sham feeding profiles of the four groups with the sucrose concentrations used. Analysis of variance indicated that groups differed in their level of sham feeding, F(3,17)=4.78, p<0.01, and that consumption was influenced greatly by sucrose concentration, F(3,51)=95.6, p <0.0001. However, the profiles of group intake change with ascending sucrose concentration were not different, F(9,51)= 1.26, p >0.05. Multiple comparisons using the Studentized range statistic and evaluated with the Newman-Keuls procedure (51 df) indicated that VMH rats sham fed equivalent 6% sucrose as

controls 09>0.05), but consumed more 12% (/9<0.01), 18% 09<0.01) and 24% 09<0.05) than controls. ST animals also sham fed more than controls at all sucrose concentrations including 6% 09's<0.01). At 6% sucrose, ST rats sham fed even more than VMH animals 09<0.05). ST and VMH rats sham fed similar amounts of 12, 18 and 24% sucrose 09>0.05). Animals in the VMH/ST group consumed more than controls at all sucrose levels 09's<0.01). Furthermore, they sham fed more than VMH rats at all four sucrose concentrations. This difference was significant for 6, 12 and 24% sucrose 09<0.05) but not at 18% 09>0.05). VMH/ST rats ate significantly more than ST rats at 24% sucrose 09<0.05). DISCUSSION The present experiment replicates previous reports that VMH lesions result in disproportionately large increases in sham feeding as the sweetness of the diet increases (39,41). Since these results are obtained with sham feeding, they suggest an exaggerated reactivity to the sensory aspects of food in VMH rats. Furthermore, this study demonstrates for the first time that rats with ST transections, which do not involve the VMH, show similar disturbances of sham feeding. In fact, the exaggeration of sham feeding in rats with ST cuts is as great as that seen in VMH animals. The only difference is that ST rats increase sham feeding relative to controls at lower sucrose concentrations than do VMH rats. The data most relevant to evaluating the present hypothesis are those of rats with combined VMH lesions and ST knive cuts. These rats demonstrate the largest perturbation of sham feeding relative to controls; they consume more than either VMH or ST alone animals. This finding suggests that the taste disturbance induced by VIVIHdamage does not require damage to amygdalo-hypothalamic connections. If this

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hypothesis were correct, combined VMH/ST rats should sham feed no more than either VMH or ST alone rats, and this result is not obtained. E X P E R I M E N T 2: S H A M F E E D I N G Q U I N I N E ADULTERATED SOLUTIONS To characterize more fully the taste reactivity changes produced by ST, VMH, or the combined damage, food intake adjustments to hedonically negative taste manipulations were also examined. Although VMH rats overeat hedonically positive diets, they do not show an exaggerated rejection of bitter tasting diets when they are maintained at control body weights (10, 11, 28). This asymmetrical nature of finickiness of VMH rats is evident in sham feeding probes of taste reactivity as well. Specifically, although VMH rats sham feed more 30% sucrose than controls (39), they show control-like decreases of sham feeding with increasing quinine concentration (40). It is not known how an ST rat, which shows exaggerated sham feeding of sweet solutions, would react to adulteration of its diet with unpalatable tastes. METHOD Thirty subjects weighing a mean of 359-+6 g at surgery were used. The test diet was 30% sucrose solution adulterated with 0.0, 0.001, 0.0025, or 0.005% quinine hydrochloride (weight/vol). All rats were trained initially to sham feed reliably with 30% sucrose. Rats were never exposed to quinineadulterated solutions on two consecutive days. RESULTS Eight of nine rats that received VMH lesions had sufficient damage to be included in this group. Five of six rats

sustained criterion bilateral transections of the ST. Three of nine rats with criterion damage to both the VMH and ST constituted the VMH/ST group. Of six control rats, two failed to sham feed reliably and were not included in the analyses. Weights did not differ significantly between groups either at the start, F(3,16)=1.30, p>0.05, or end, F(3,16)=0.85, p >0.05, of testing. Figure 3 shows the sham feeding profiles across the various quinine concentrations. Not unexpectedly, quinine concentration significantly affected the amount sham fed, F(3,48)=19.49, p<0.0001. Group differences were also apparent, F(3,16)=5.28, p<0.01. The patterns of intake changes across the quinine concentrations, however, were not different among the groups, F(9,48)=0.82, p>0.05. Multiple comparisons (48 dJ) showed that at 0.0% quinine (unadulterated 30% sucrose), both VMH and ST rats sham fed significantly more than controls (p's<0.05), but were not different from each other (p's>0.05). Also, on this solution, VMH/ST rats sham fed significantly more than all other groups (p's<0.05). All groups significantly decreased intake as the quinine concentration increased from 0.0% to 0.005%. The amount of reduction was similar. VMH rats decreased their intake by 12.5-+3.1 ml; controls, 11.8-+4.1 ml; ST rats 15.6-4.5 ml; and VMH/ST rats 14.2-+9.3 ml. These group differences were not significant, F(3,16)---0.13, p>0.05. DISCUSSION The sham feeding pattern observed at 0% quinine (unadulterated 30% sucrose) replicates that seen in Experiment 1: VMH/ST rats sham feed more than either V M H or ST animals, and all three of these groups consume more than controls. However, the present results show no difference

VMH, ST, AND TASTE REACTIVITY among the groups in their responsiveness to quinine; all groups show similar reductions of sham feeding with increas, ing quinine concentration. EXPERIMENT 3: NORMAL FEEDING (CLOSED CANNULA) TESTS ST, VMH and VMH/ST rats overrespond to sweet, but not bitter, tastes in a sham feeding test. While the nature of the sham feeding situation is ideal to allow certain insights into taste-driven feeding behavior, it is not directly obvious how performance in sham feeding tests will manifest in the eating situation of interest, i.e., normal feeding. VMH rats, which overconsume sweet-tasting foods in sham feeding tests, maintain the hyperphagia on these foods when eating normally (39). Although ST rats are as disturbed in sham feeding as VMH rats, it is not known how much they eat in normal situations. This experiment compares the intakes of ST, VMH and VMH/ST rats eating normally under the same test conditions in which a sham feeding disturbance was identified. METHOD

705 reactivity to the positive sensory properties of the solutions being consumed. From this perspective, the behavior of the ST rats is enigmatic, In spite of an increased sham fed intake, ST rats do not overeat under similar experimental conditions if they are eating normally. Thus, the feeding behavior disturbance of sham feeding ST rats is masked or eliminated when the continuity of the gastrointestinal tract is restored by closing the cannula. In fact, ST transections attenuate the degree of hyperphagia produced by VMH lesions. EXPERIMENT 4: AD LIB FOOD INTAKE AND WEIGHT GAIN In brief (30-min) exposure tests, ST knife cuts result in no overeating and attenuate the hyperphagia induced by VMH lesions. This experiment extends these observations by examining long-term ad lib food intake and weight gain in ST, VMH, and VMH/ST rats maintained on a series of conventionally-used lab diets. METHOD

Thirty rats, weighing 384_+7 g at surgery, were prepared with gastric cannulae and subject to stereotaxic surgery to produce VMH, ST, VMH/ST, and control groups. Animals were tested in a manner similar to Experiment 1 except that the cannula was closed after the stomach was cleaned. Thus, ingested food remained in the alimentary tract. Rats were tested with 6, 12, 18, and 24% sucrose which were presented, one solution per day, in random order.

Thirty-eight subjects, weighing 352_+4 g at the beginning of the experiment, were divided into four groups (VMH, ST, ST/VMH, controls). Rats were maintained ad lib on the following test diets presented for the days indicated: Purina rat chow powder (3.61 kcal/g; days 1-15); mash (65% water, 35% chow; 1.26 kcal/g; days 16-34); and high fat (33% Crisco oil, 67% chow; 5.50 kcal/g; days 35-54). Rats were 24 hr food deprived following stereotaxic surgery. Daily measurements of food intake and body weight were taken beginning on the third day after surgery.

RESULTS

RESULTS

Based upon the criteria described, 5 of 9 rats comprised the VMH group, 5 of 6 the ST group and 6 of 9 the VMH/ST group. There were 5 controls. The food restriction regimen employed was successful in maintaining equivalent body weights in the four groups. Analyses indicated that mean group weights did not differ significantly at either the start, F(3,17) = 0.82, p > 0.05, or end, F(3,17)=0.76, p>0.05, of testing. Figure 4 shows the cumulative 30 min intakes for the four groups at each sucrose concentration. As with sham feeding, the amount eaten increased significantly with ascending sucrose concentration, F(3,51)=85.8, p<0.0001. Significant group differences were also apparent, F(3,17)=5.53, p <0.01, and the pattern of intake change across concentration differed in the groups, F(9,51)=5.32, p<0.001. Multiple comparisons (51 df) revealed that all four groups consumed similar amounts of 6% sucrose (all p's>0.05). At higher concentrations, however, VMH rats ate significantly more than the three other groups (p's<0.05). In contrast to the sham feeding results, ST rats did not differ from controls at any sucrose concentration. In fact, ST damage attenuated the hyperphagia produced by VMH lesions; VMH/ST rats ate no more than ST and control animals at 6 and 12% sucrose, although their intakes were elevated relative to these groups at 18 and 24% sucrose (p's<0.01).

Based upon the criteria described, eight of 12 rats comprised the VMH group, seven of eight the ST group and six of 12 the VMH/ST group. There were six controls. At the time of stereotaxic surgery, there were no group weight differences, F(3,23)--0.17. Figure 5 shows the average daffy caloric intakes of the groups. Groups ate significantly different amounts of the powdered diet, F(3,56)=46.94, p<0.0001. Multiple comparisons showed that VMH rats ate significantly more than control, ST and VMH/ST rats (p's<0.01). VMH/ST rats were hyperphagic compared to control 09<0.05) and ST (/9<0.01) rats. ST and control rats did not differ (p>0.05). On the mash diet, large group differences in consumption were apparent, F(3,76)=29.54, p<0.0001. VMH rats continued to eat more than all other groups (p's<0.01). VMH/ST rats were still hyperphagic compared to control and ST rats (p's<0.01). ST rats ate significantly less than controls (p<0.01). Significant group differences in intake continued in the high fat period, F(3,76)=29.54,p0.05). These differences in intake were generally reflected in weight changes (Fig. 6). Although a significant group effect was apparent upon analysis of group mean weights at the end of the powder period, F(3,23)=3.09, p<0.05, multiple comparisons revealed that only the VMH versus ST palrwise comparison was significant, p<0.05. By the end of the mash period, however, a large and significant difference in weight

DISCUSSION Consistent with similar findings (39,40), the enhanced intake of VMH rats is apparent in both 30-minute normal and sham-feed tests. This hyperphagia during normal feeding is generally interpreted as reflecting a lesion-induced hyper-

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existed, F(3,23)= 18.65, p<0.0001. VMH rats weighed more than any other group (p's<0.01) and VMH/ST rats weighed more than both control (p<0.05) and ST (p<0.01) rats. ST and control rats did not differ in weight. At the end of access to high fat diet, groups still differed significantly in weight, F(3,23)=17.32, p<0.01. VMH rats weighed more than control and ST rats (p's<0.01) but not more than VMH/ST rats. VMIadST rats also weighed more than control and ST rats (p's<0.01). ST and control group weights did not differ (p >0.05).

DISCUSSION

The ad lib food intake data parallel the results from the 30-minute normal feed tests. Specifically, and not surprisingly, VMH rats are hyperphagic on the diets used. In contrast, ST rats eat no more, and gain no more weight, than controls in spite of the marked difference between these groups in sham feeding. In fact, as in Experiment 3, ST knife cuts attenuate the hyperphagia and consequent weight gain resulting from VMH lesions.

VMH, ST, AND TASTE REACTIVITY

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(wt/vol)

FIG. 7. Thirty rain sham fed intakes from Experiments 1 (top graph) and 2 (lower graph). The "predicted" curve is that generated by adding the effects of VMH lesions and ST knife cuts. G E N E R A L DISCUSSION These experiments were conducted to investigate the hypothesis that interruption of amygdalo-hypothalamic connections via the ST mediates the taste processing disturbances associated with VMH destruction. The results obtained do not support the hypothesis. This is most evident in Experiments 1 and 2 which compare the degree of taste reactivity in rats with combined VMH/ST ablation to those with either VMH or ST damage alone. If disruption of amygdalo-hypothalamic connections produces VMH finickiness, then completely interrupting these connections at two points, at the VMH itself and at some point remote from the VMH, should produce an effect no different than interrupting the connections at one of these points only. However, the magnitude of sham feeding disturbance in VMH/ST rats is equal to the sum of those produced by VMH and ST damage alone. This is shown most clearly in Fig. 7, which presents the sham feeding profiles of VMH, ST and VMH/ST groups for Experiments 1 and 2. Based upon the performance of animals with VMH or ST damage, a curve is calculated which predicts the performance of animals if these two effects are independent and additive. The actual data obtained in VMH/ST rats are compared to this predicted curve and, as seen in Fig. 7, the sham feeding prof'de observed in VMH/ST rats closely tracks that predicted. The independent nature of ST and VMH effects is also seen in normal feeding tests, where ST damage does not mimic the effects of VMH

lesions, but, rather, attenuates the hyperphagia and weight gain effects of VMH lesions. Rats with ST knife cuts display an altered reactivity to tastes in the sham feeding situation. When sham feeding hedonically positive solutions, the intake of ST rats was two to three times that of controls (Experiments 1 and 2). This degree of disturbance is as marked as that of VMH lesions. Neither VMH nor ST rats appear to overrespond to hedonically negative taste manipulations. Since sham feeding eliminates or minimizes postingestional factors, the altered sham feeding profile of ST rats may reflect a change in taste responsivity in ST rats similar in magnitude and kind to that of VMH rats. We note, however, that the sham feeding profiles of ST and VMH rats are not identical. VMH lesions, as reported elsewhere (39,41), result in disproportionately large increases of sham feeding as the sweetness of the diet increases. In contrast, ST lesions elevate overall Sham fed intake; but, the profile across sucrose concentrations parallels controls. This difference may reflect differing mechanisms underlying VMH- and ST-induced taste hyperreactivity. Some consider the taste reactivity of the VMH rat as a primary cause of its hyperphagia [e.g., (29)] and the dissociation between ST effects on sham and normal feeding may lead one to question this hypothesis. However, since the mechanisms underlying the taste reactivity in VMH and ST animals may differ, it is unclear how relevant the dissociation observed in the ST rat is to an understanding of VMH lesion-induced hyperphagia. It may also be that some disturbance of eating persists in the normally-feeding ST rat but it is not one reflected in changes of ad lib intake or weight maintenance (the only parameters of normal feeding measured here). A more fine-grained analysis of feeding behavior might reveal a change in meal pattern or structure in ST rats. Or, similar to the finding of amygdala effects on drinking behavior, for example, deficits in ST rats may be apparent only in response to various homeostatic challenges (34). A change in taste processing resulting from ST damage is consistent with current descriptions of extensive projections of taste systems from the hind-brain to forebrain (24, 27, 31, 45). Three forebrain areas receive the majority of projections from the hind- and midbrain gustatory areas: the amygdala, medial hypothalamus, and bed nucleus of the stria terminalis (25,31). Given the central role of the ST as the major pathway linking these three areas (7,8), it is reasonable that damage to this pathway might produce changes in taste-driven intake. Unfortunately, little is known about the behavioral function of the forebrain taste systems (16, 17, 26). The magnitude of taste processing disturbance in ST animals documented here is one of the more dramatic demonstrations of an eating-related dysfunction resulting from manipulation of forebrain taste projections. However, beyond the demonstration that a forebrain manipulation can influence the ability of tastes to drive intake, the present study provides few clues as to why or how ST transections produce this behavior change. One is optimistic, however, that a more thorough investigation of the sham feeding changes observed in ST animals might provide insight into the function of the forebrain taste systems. ACKNOWLEDGEMENTS This research was supported by the Natural Sciences and

Engineering Research Council of Canada. Some of these data were presented at the 17th Annual Meeting of the Society for Neurosciences, New Orleans, October, 1987.

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