Ventromedial hypothalamic lesions abolish compensatory reduction in energy expenditure to weight loss.

Weight loss through caloric restriction produces compensatory reductions in the whole body energy expenditure of normal rats. The present experiment determined whether rats who had become obese after ventromedial hypothalamic (VMH) lesions displayed this metabolic defense of body weight. Obese VMH-lesioned and normal-weight control female rats were assigned to one of three weight maintenance conditions (100, 90, and 80% of previously maintained body weight). Postabsorptive oxygen consumption was then measured by open-circuit respirometery while, simultaneously, behavioral activity was measured by stabilimeter. A marked decline in resting energy expenditure and behavioral activity, seen in control rats after weight loss, was absent in VMH-lesioned rats. These results suggest that VMH lesions impair the ability to adjust energy expenditure in response to alterations in nutritional status, a response that normally serves to stabilize body weight at a regulated level.

The pharmacology of endorphin modulation of chick distress vocalization.

Intraventricular injections of beta-endorphin, gamma-endorphin and alpha-endorphin were demonstrated to reduce isolation-induced distress vocalization on 2-4 day old chicks in a dose response manner at doses as small as 12.5 picomoles (pmol). beta-Endorphin was more potent than the other peptides and morphine, while Met-enkephalin was without effect. However, the D-Ala2 substituted form of Met-enkephalin was as potent as morphine. None of the opioid peptides was effective when injected peripherally in doses of 400 pmol/g body weight. Extension of the interval between injection and behavioral observation from 4 minutes eliminated the ability of alpha- and gamma-endorphin to reduce the peeps. Specificity of the opioid effect was determined by testing intraventricular injections (200 pmol) of 9 other endogenously found peptides. Somatostatin, vasoactive intestinal peptide, and human pancreatic peptide reduced the vocalizations modestly, while alpha-MSH reliably increased them.

Reduced energy expenditure after ventromedial hypothalamic lesions in female rats.

Activity, O2 consumption, and body composition were measured in female rats with lesions of the ventromedial hypothalamus (VMH). One group of lesioned rats was food restricted to maintain body weights at control levels. O2 consumption of these food-restricted VMH-lesioned rats was 13% lower than that of nonlesioned rats. About half this energy savings accrued from reduced activity; the remainder resulted from a decline in resting metabolic rate (RMR). Though matched in weight to controls, the body composition of the restricted VMH-lesioned rats was abnormal. Their carcass protein was reduced by 12%, whereas fat was elevated 200%. The replacement of lean metabolically active tissue by carcass fat appears to underlie the reduction in RMR, an interpretation supported by multiple-regression analysis of carcass composition. Ad libitum-fed VMH-lesioned rats did not show this carcass protein decline, though their fat was elevated 895%. These results confirm that reduced activity contributes to energy savings and weight gain after VMH lesions. Likewise, restricting weight of VMH-lesioned rats to control levels reduced RMR, apparently because carcass protein declines. But, since ad libitum-fed female VMH-lesioned rats do not display reduced carcass protein, the historic assumption that RMR reductions contribute to their obesity appears unwarranted.

Effects of alpha-MSH on motivation, vigilance and brain respiration.

In a series of experiments designed to assess the effects of alpha-MSH on various motivational processes, it was observed that the hormone can slightly decrease food intake and increase water consumption during the first hr after administration in rats. alpha-MSH also modified avoidance behavior in 1- and 3-day-old chicks, but there were no reliable effects on activity, distress vocalizations and the tonic immobility response. alpha-MSH appeared to modulate the sleep-waking activity of rats, and the most prominent effect was an increase of slow wave sleep during the 2-3 rd hr after treatment. A possible second effect was a homogenization of sleep patterns--with poor sleepers exhibiting increases of activated sleep and good sleepers a reduction. Measurement of in vitro brain oxygen consumption indicated that mice treated with alpha-MSH exhibit an 18% reduction in respiration of the brain stem section which includes the locus coeruleus, but did not reliably change respiration in forebrain cortices. alpha-MSH also produced a modest 14% increase of plasma glucose. These results are discussed in terms of possible modulation by alpha-MSH of activity in central autonomic cell groups such as the locus coeruleus.

Effects of ovariectomy and estradiol injections on food intake and body weight in rats with ventromedial hypothalamic lesions.

Female rats with lesions of the ventromedial hypothalamus (VMH) were ovariectomized during the static obese stage after body weight levels had stabilized. Following ovariectomy, rats with VMH lesions showed smaller increases in food intake and less body weight gain than non-lesioned controls ovariectomized at the same time. Subsequently, the effects of peripheral injections of estradiol benzoate (EB) on feeding and body weight were examined. Ovariectomized rats with VHM lesions were also less responsive to exogenous EB treatment; they lost significantly less weight in response to estrogen than controls. EB caused a somewhat smaller reduction in food intake by the VMH group but this difference was not significant. Considered together the available data on changes in responsiveness to endogenous and exogenous estrogen following VMH lesions suggest a role for VMH estrogen receptors in the regulation of body weight, but these estrogen receptors may not modulate weight by directly altering food intake as previously suggested.

Behavioral changes following VMH lesions in rats with controlled insulin levels.

The effects of ventromedial hypothalamic (VMH) lesions were studied in female rats made diabetic with streptozotocin that were given twice daily injections of protamine zinc insulin (0.75 mu/100g/day) and in non-diabetic animals of the same sex. Hyperphagia resulted from VMH lesions in both diabetic animals whose insulin levels were controlled and in non-diabetic animals. All animals with lesions exhibited persistent increases in feeding during the light protion of the light-dark cycle. Significant increases in body weight gain were observed in both diabetic and non-diabetic lesioned animals, but the magnitude of wegith gain was greater after VMH lesions in non-diabetic rats. VMH lesions also reduced wood-gnawing and increased emotionality, aversion to quinine and reactivity to electric shock. None of the behavioral changes were dependent on hyperinsulinemia, although hyperinsulinemia may contribute to the magnitude of certain of these effects.