BEHAVIORAL BIOLOGY 19, 394--400 (1977), Abstract No. 6229

BRIEF REPORT

Hyperphagia and Obesity in the Guinea Pig Produced by Hypothalamic Knife Cuts 1

ANTHONY SCLAFANI AND MARK SPERBER

Department of Psychology, Brooklyn College of the City University of New York, Brooklyn, New York 11210

Bilateral parasagittal knife cuts were placed between the medial and lateral hypothalamus of adult male and female guinea pigs. In both sexes, the knife cuts increased food intake, water intake, and body weight relative to control animals given sham surgery. The results demonstrate that hypothalamic hyperphagia and obesity can be produced in the guinea pig as in other species.

Damage to the ventromedial hypothalamus (VMH) results in hyper- phagia and obesity in a variety of species including the rat, mouse, dog, cat, hamster, monkey, goat, sparrow, and man (Anand, Dua, and Shoen- berg, 1955; Baile, Mayer, Mahoney, and McLaughlin, 1970; Bray and Gallagher, 1975; Brobeck, Tepperman, and Long, 1943; Heinbecker, White, and Rolf, 1944; Kuenzel, 1972; Marks and Miller, 1972; Mayer, French, Zighera, and Barnett, 1955). A notable omission to this list is the guinea pig. In the only study reported to date, Joseph and Knigge (1968) found that bilateral electrolytic lesions of the VMH do not increase food intake and body weight in newborn or adult guinea pigs. The failure to obtain hypothalamic obesity in this species may indicate that the neural control of food intake is uniquely different in the guinea pig, or that the herbivorous feeding habit of this animal makes hyperphagia difficult to display (Hirsch, 1973). Alternatively, as Joseph and Knigge (1968) point out, their lesions may not have increased food intake because the lesions were limited to the ventromedial nuclei (VMN), and the hyperphagic effect may be due to damage to tissue adjacent to the VMN. This possibil- ity is supported by the recent observation that restricted VMN lesions also fail to produce obesity in rats (Gold, 1973). The present experiment, therefore, reexamined the effects of medial hypothalamic damage on the food intake and body weight of guinea pigs. In this case, parasagittal knife cuts, rather than electrolytic lesions, were used. Such cuts have been found to reliably induce overeating and obesity in rats when appropriately

1 This research was supported by National Institute of Mental Health Grant MH 21563 and by the Research Foundation of the City University of New York, Grant 10103.

394 Copyright © 1977 by Academic Press, Inc. All rights of reproduction in any form reserved. ISSN 0091-6773

HYPERPHAGIA AND OBESITY IN GUINEA PIGS 395

placed between the medial and lateral hypothalamus (e.g., Sclafani, 1971).

Eight male and eight female adult guinea pigs (Hartley strain, Perfec- tion Breeders) with mean body weights of 910 and 720 g, respectively, were used. The animals were individually housed in wire-mesh cages (40.6 x 24.1 x 17.8 cm) kept in an air-conditioned (21 + I°C) colony maintained on a 12-hr light-dark cycle. The subjects were given Purina Guinea Pig Chow and tap water, and food intake, water intake, and body weight were measured daily. Bilateral parasagittal knife cuts were made in five male and four female animals using the encephalotomy procedure described by Sclafani (1971), whereas sham knife cuts were made in the remaining subjects. With the skull level, the guide shaft of the knife was positioned 2.5 mm anterior to bregma, 3.5 mm above the base of the brain, and 0.9 mm lateral to the midline. A 3-mm length of cutting wire was extended in a caudal direction, and the parasagittal cut was made by lowering the knife to the base of the brain. Histological analysis revealed that the knife cuts varied slightly in their position, but all were just medial to the fornix bundle and extended from the anterior hypothalamus to the premamillary region (Fig. 1). These cuts are similar to those that were found effective in producing hyperphagia and obesity in the rat (Sclafani, 1971).

The behavioral findings are summarized in Figs. 2 and 3. Preopera-

FIG. 1. Photomicrograph from a female rat given bilateral parasagittal knife cuts be- tween the medial and lateral hypothalamus.

396 SCLAFANI AND SPERBER

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FIG. 2. Mean food intake, water intake, and body weight of male guinea pigs given bilateral hypothalamic knife cuts (CUT group) or sham surgery (CON group) at the point indicated by the arrow. Intake measures represent means of 5-day periods, and body weight data are based on the last day of each period.

tively, there were no significant differences between the experimental and control groups on either intake or body weight measures. Following surgery, the knife-cut male and female guinea pigs increased their food intake, whereas the sham-operated animals showed little or no change in their food intake. This difference was not significant for the first 5-day period after surgery, but, by the second 5-day period, the knife-cut rats ate reliably (P < 0.05, t-test) more food than did the controls, and their

HYPERPHAGIA AND OBESITY IN GUINEA PIGS 397

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FIG. 3. Mean food intake, water intake, and body weight of female guinea pigs given bilateral hypothalamic knife cuts (CUT group) or sham surgery (CON group) at the point indicated by the arrow. Intake measures represent means of 5-day periods, and body weight data are based on the last day of each period.

intakes remained elevated (P < 0.05) for the remaining 20 days of the experiment.

As a result of their increased food consumption, the knife-cut animals gained significantly (P < 0.05) more weight during the 30-day postopera- tive observation period than did the sham-operated controls. The female cut subjects gained 177.6 g (range = 97-220 g) during this time compared to the 70.8 g (range = 42-105 g) gain of the female controls, and the male cut animals gained 181.6 g (range = 141-234) compared to the 91.0 g

398 SCLAFANI AND SPERBER

(70-116 g) gain of the male controls. The absolute weight gains displayed by the male and female guinea pigs given knife cuts were, therefore, very similar (181.6 vs 177.6), although, when compared to the control baselines, the females showed a 151% increase in weight gain, whereas the males displayed a 99% increase in weight gain. These results agree with the recent findings that VMH cuts or lesions produce similar weight gains in male and female rats (Gold, 1970; Rehovsky and Wampler, 1972). Thus, in contrast to the earlier belief that a sex difference exists in hypothalamic obesity (Cox, Kakolewski, and Valenstein, 1969), VMH damage appears, instead, to attenuate the sex difference in the growth rates normally seen in rats and guinea pigs. Since the rate of growth of intact males exceeds that of females, however, hypothalamic obesity is more obvious in female than in male animals.

In addition to their elevated food intake, the knife-cut guinea pigs drank considerably more water than did the control subjects (females: P < 0.01, t-test; males: P < 0.06, t-test, P < 0.02, U-test). One male and two female guinea pigs with knife cuts were extremely hyperdipsic with mean post- operative water intakes of 372, 327, and 447 ml/day. Five other cut subjects were moderately hyperdipsic with mean intakes ranging from 181 to 297 ml/day, and the two remaining male guinea pigs were slightly hyperdipsic with mean intakes of 145 and 155 ml/day. The water intakes of the sham-operated animals ranged from 61 to 115 ml/day. The in- creased water consumption of the knife-cut subjects was not completely secondary to their increased food intake, since their postoperative water to food intake ratios exceeded that of the controls (females: 4.01 vs 1.85 ml/g, respectively; males: 3.36 vs 2.14 ml/g, respectively), although these differences reached significance only for the female animals (P < 0.01). The parasagittal knife cuts, therefore, appeared to have a direct effect on water intake and most likely produced diabetes insipidus in several ani- mals.

The present findings demonstrate that guinea pigs are similar to many other animal species in that they display hyperphagia and obesity follow- ing appropriate damage to the medial hypothalamus. Thus, the failure of Joseph and Knigge (1968) to obtain hyperphagia and obesity was probably due to their use of lesions restricted to the VMN. Recent studies now indicate that the feeding effects of VMH lesions or knife cuts result from the transection of a longitudinally situated pathway which passes just lateral and anterior to the VMN (Gold, 1973; Sclafani and Berner, 1977).

Although the hyperphagia and obesity displayed by the guinea pigs given knife cuts were not as great as that typically seen in rats, it should be noted that, in the present experiment, the group sizes were small, no experimental animals were excluded, and the diet was not highly palat- able. Most likely, under more favorable conditions, greater hyperphagia and obesity can be obtained in guinea pigs.

HYPERPHAGIA AND OBESITY IN GUINEA PIGS 399

Finally, the feeding behavior of the guinea pig has not been extensively studied (Hirsch, 1973; Hirsch & Collier, 1974; Joseph and Knigge, 1968; Reisbick, 1973), although this species has several distinct advantages over other commonly used laboratory animals (see Jonson, Lyle, Edwards, and Penny, 1975). Further and more detailed study of the hypothalamic control of food intake and body weight in the guinea pig is, therefore, warranted and may help to define the generality of the extensive research findings obtained with the rat.

REFERENCES Anand, B. K., Dua, S., and Shoenberg, K. (1955). Hypothalamic control of food intake in

cats and monkeys. J. Physiol. 127, 143-152. Baile, C. A., Mayer, J., Mahoney, A. W., and McLaughlin, C. (1970). Hypothalamic

hyperphagia in goats and some observations of its effect on glucose utilization rate. J. Dairy Sci. 53, 801-807.

Bray, G. A., and Gallagher, T. F. (1975). Manifestations of hypothalamic obesity in man: A comprehensive investigation of eight patients and a review of the literature. Medicine 54, 301-330.

Brobeck, J. R., Tepperman, J., and Long, C. N. H. (1943). Experimental hypothalamic hyperphagia in the albino rat. Yale J. Biol. Med. 15, 831-853.

Cox, V. C., Kakolewski, J. W., and Valenstein, E. S. (1969). Ventromedial hypothalamic lesions and changes in body weight and food consumption in male and female rats. J. Comp. Physiol. Psychol. 67, 320-326.

Gold, R. M. (1970). Hypothalamic hyperphagia: Males get just as fat as females. J. Comp. Physiol. Psychol. 71, 347-356.

Gold, R. M. (1973). Hypothalamic obesity: The myth of the ventromedial nucleus. Science 182, 488-490.

Heinbecker, P., White, H. L., and Rolf, D. (1944). Experimental obesity in the dog. Amer. J. Physiol. 141, 549-565.

Hirsch, E. (1973). Some determinants of intake and patterns of feeding in the guinea pig. Physiol. Behav. 11, 687-704.

Hirsch, E., and Collier, G. (1974). The ecological determinants of reinforcement in the guinea pig. Physiol. Behav. 12, 239-249.

Jonson, K. M., Lyle, J. G., Edwards, M. J., and Penny, R. H. C. (1975). Problems in behavioural research with the guinea pig: A selective review. Anita. Behav. 23, 632- 639.

Joseph, S. A., and Knigge, K. M. (1968). Effects of VMH lesions in adult and newborn guinea pigs. Neuroendoerinology 3, 309-331.

Kuenzel, W. J. (1972). Dual hypothalamic feeding system in a migratory bird, Zonotrichia albicollis. Amer. J. Physiol. 223, 1138-1142.

Marks, H. E., and Miller, C. R. (1972). Development of hypothalamic obesity in the male golden hamster (Mesocricetus auratus) as a function of food preference. Psychon. Sci. 27, 263-265.

Mayer, J., French, R. G., Zighera, C. F., and Barnett, R. J. (1955). Hypothalamic obesity in the mouse. Amer. J. Physiol. 182, 75-83.

Rehovsky, D. A., and Wampler, R. S. (1972). Failure to obtain sex differences in develop- ment of obesity following ventromedial hypothalamic lesions in rats. J. Comp. Physiol. Psychol. 78, 102-112.

Reisbick, S. H. (1973). Development of food preferences in newborn guinea pigs. J. Comp. Physiol. Psychol. 85, 427-442.

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Sclafani, A. (1971). Neural pathways involved in the ventromedial hypothalamic lesion syndrome in the rat. J. Comp. Physiol. Psychol. 77, 70-96.

Sclafani, A., and Berner, C. N. (1977). Hyperphagia and obesity produced by parasagit- tal and coronal hypothalamic knife cuts: Further evidence for a longitudinal feeding inhibitory pathway. J. Comp. Physiol. Psychol., in press.