VMH-lesioned Rats Research Articles

Pituitary-adrenocortical response to shock-induced stress in normal and hypothalamic hyperphagic rats

Several previous experiments have reported that mediobasal hypothalamic lesions that include the ventromedial nuclei result in decreased adrenal weights and impaired pituitary-adrenocortical responses to stress. In the present experiment, lean and obese rats with lesions of the ventromedial hypothalamus that spared the median eminence were found to have normal adrenal weights and normal elevations in plasma corticosterone to shock-induced stress. The previous results were attributed to incidental damage to adjacent structures, particularly the median eminence. Lean but not obese VMH-lesioned rats were found to have higher baseline corticosterone levels.

The effects of estradiol on body weight and food intake in normal weight VMH-lesioned rats

The effects of estradiol on food intake and body weight were examined in ovariectomized and VMH-lesioned, ovariectomized rats that were prevented from supranormal weight gain by food restriction. Estradiol injections that were effective in reducing weight in supranormal weight, ovariectomized rats had no effect on weight in normal weight, ovariectomized or VMH-lesioned, ovariectomized rats. Estradiol did not prevent hyperphagia and weight gain in VMH-lesioned, ovariectomized rats when they were provided with ad lib food.

Appetite suppression caused by CCK is diet specific in VMH-lesioned rats

Intraperitoneal injections of the C-terminal octapeptide of cholecystokinin-pancreozymin (CCK) failed to inhibit 5.5-h-fasted feeding of a high-fat diet in rats with electrolytic lesions of the ventromedial hypothalamus. Similar injections significantly reduced the intake of a high-fat diet in sham-lesioned controls. These results are consistent with Powley’s (1977) cephalic phase hypothesis (CPH) and are interpreted to mean that rats with electrolytic lesions of the ventromedial hypothalamus, when given a highly palatable diet, demonstrate a prolonged cephalic reflex, which results in metabolic disturbances which may override the effect of CCK at the 40 U/kg dose.

Hyperphagia and obesity following ventromedial hypothalamic lesions in rats with subdiaphragmatic vagotomy

Bilateral subdiaphragmatic vagotomy chronically reduced body weight to 85–90% of sham vagotomy weight levels in female rats maintained on a standard pellet diet (observed for 114 days). Ventromedial hypothalamic lesions 70 days after vagotomy resulted in marked hyperphagia and obesity, although the increases were not as great as those following lesions in nonvagotomized animals. When the order of surgery was reversed, vagotomy reduced the body weight of obese VMH-lesioned rats to vagotomized control levels, with no evidence of recovery after 90 days. These results suggest that while enhanced vagal activity and/or vagally mediated hyperinsulinemia contribute to VMH lesion-induced overeating and weight gains, they are not necessary for the manifestation of either the hyperphagia or obesity. The importance of adaptation to the effects of vagal transections for the appearance of hypothalamic hyperphagia and obesity is discussed.

Some effects of ventromedial hypothalamic lesions, adrenalectomies, and corticosterone replacement therapy on energy expenditure in rats

The present study tested the hypothesis that the decreases in energy expenditure reported following ventromedial hypothalamic (VMH) lesions in rats are a function of the decreases in adrenal function. Five groups of rats received 21 1hr/day sessions in activity wheels and then were subjected to either VMH lesions, adrenalectomies, the respective sham-operations, or no operation. Following surgery, each rat was again given access to an activity wheel for 24 1-hr test sessions. During the test phase the rats received a sequence of drug/no drug conditions which consisted of: (1) no injection; (2) injections of the vehicle substance; or (3) injections of corticosterone in the vehicle substance. Under the no-drug conditions, running levels of the VMH-lesioned and adrenalectomized rats decreased, with the levels of VMH-lesioned rats being more severely depressed. Corticosterone replacement therapy reinstated the activity levels of the adrenalectomized rats, but not those of the VMH rats. The hypothesis that the reductions in activity following adrenalectomy or destruction of the VMH are due to disruption of the same mechanism was not supported.

Consequences of ventromedial hypothalamic lesions on metabolism of perfused rat liver.

Metabolism of perfused livers from control and ventromedial hypothalamus (VMH)-lesioned rats has been studied. To eliminate the possibility that observed metabolic abnormalities could be realted to hyperphagia, VMH-lesioned rats were placed on restricted diet matching that of controls. Ten days postoperatively, VMH-lesioned rats had hyperinsulinemia, hypertriglyceridemia, increased blood urea nitrogen levels, together with decreased plasma free fatty acid (FFA) and glucose levels. Insulin release produced in vivo by a glucose load was much higher in VMH-lesioned than in control rats. Perfused livers from VMH-lesioned rats secreted more triglycerides and produced more urea than controls, whereas production of glucose and ketone bodies was reduced. Lipogenesis, newly synthesized triglyceride secretion, and the activity of acetyl-CoA carboxylase and fatty acid synthetase were greatest in livers from VMH-lesioned rats. Fasting abolished hyperinsulinemia and most of these observed metabolic alterations. After treatment with anti-insulin serum, the high rate of lipogenesis observed in livers from VMH-lesioned rats was restored toward normal. It is suggested that hyperinsulinemia may be partly responsible for the metabolic disorders observed in livers from nonhyperphagic VMH-lesioned rats.

Response to glucoprivic and hydrational challenges by normal and hypothalamic hyperphagic rats

Obese VMH-lesioned rats displayed normal, but delayed, increases in food intake to 350 mg/kg 2-deoxy-D-glucose (2-DG) and were hyperresponsive to 4 and 8 U of insulin. Lesioned rats maintained at preoperative body weight responded normally to insulin, but did not increase food consumption to 350 mg/kg 2-DG. Both lean and obese lesioned rats decreased feeding following 750 mg/kg 2-DG. The lesioned animals displayed either no change or an increase in water/food ratios. Those with normal water/food ratios showed a loss in circadian control of water intake and drank less than controls during food deprivation. VMH-lesioned rats responded normally to polyethylene glycol and were hyperresponsive to hypertonic saline regardless of differences in body weight or water/food ratios. The possibility of ventromedial hypothalamic damage producing a general increase in responding, or numerous more specific effects, is discussed.

The Effects of Subdiaphragmatic Vagotomy in Rats With Ventromedial Hypothalamic Obesity

The present study investigated the effects of subdiaphragmatic vagotomy in rats with ventromedial hypothalamic (VMH) lesions and obesity. Vagotomy or sham-vagotomy was performed two weeks after VMH lesions and rats were observed for 4 more weeks. Complete vagotomy reversed the VMH obesity, lowered serum insulin, lowered basal gastric acid and blocked the secretion of gastric acid after stimulation of the cervical vagus. Pair-feeding of VMH-lesioned rats without vagotomy to the food intake of vagotomized animals also reversed the obesity, lowered serum insulin and lowered basal acid secretion, but it did not prevent the rise in acid after vagal stimulation. These results suggest that subdiaphragmatic vagotomy reversed the obesity of VMH lesioned rats primarily by decreasing food intake. However, there was a positive correlation (r = .70) between the level of serum insulin and basal gastric acid in VMH lesioned rats which remained significant when the effects of food intake were held constant (partial correlation coefficient = 0.449). This supports the possibility that ventromedial hypothalamic injury is followed by enhanced vagal activity and that the vagus may play an important part in the hyperinsulinemia of VMH obesity.

Satiety elicited by the C-terminal octapeptide of cholecystokinin-pancreozymin in normal and VMH-lesioned rats

The dose-response curve of satiety elicited by intraperitoneal injections of the synthetic C-terminal octapeptide of cholecystokinin-pancreozymin (CCK) in normal rats is U-shaped over the range 1–100 U/kg with the maximal effect at 40 U/kg. Injections of 40 U/kg also inhibited 5.5-hr-fasted feeding of rats with electrolytic lesions of the ventromedial hypothalamus. The results confirm the findings of Gibbs, Young, and Smith ( J. Comp. Physiol. Psychol. 84 , 488–495, 1973) , that injections of CCK decrease food intake of rats, and indicate that this effect of CCK is not mediated through the ventromedial hypothalamus.

Preabsorptive insulin release and hypoglycemia in rats.

Peripheral blood glucose and immunologically reactive insulin levels were determined in freely moving normal rats which were submitted either to a free oral glucose load or to a gastric administration of the glucose load. Identical determinations were performed in ventromedial hypothalamic nucleus-(VMH) lesioned and vagotomized rats after the same oral intake. It was demonstrated that: 1) a free oral glucose intake was immediately followed by two peaks of insulun release and a resultant decrease in blood glucose; 2) a gastric glucose load resulted in a single peak of insulin release and the concomitant decline in blood glucose; 3) the recorded blood glucose level was the resultant of the insulin-induced hypoglycemia and the postabsorptive hyperglycemia; and 4) the responses were largely exaggerated in VMH-lesioned rats and abolished by vagotomy. It is concluded that the early prandial insulin release reflexly induced by food-related stimuli temporarily enhances the metabolic conditions which provoke feeding.

A physiological control theory of food intake in the rat: Mark 1

The theory that current supply of readily used energy is the primary control in feeding is embodied in a computer model of energy flows from the gut and to or from storage as fat. Values for all parameters are derived from physiological data. Meal patterns and cumulative food intakes are realistically predicted for normal and VMH-lesioned rats.

Cue prominence as a determinant of VMH obesity.

Food prominence was manipulated in an attempt to test Schachter's notion that VMH obesity is caused by lesion-induced hyperresponsivity to environmental stimuli. The results indicate, contrary to Schachter's proposal, that ad lib. overeating of dynamic phase VMH-lesioned rats is not affected by the amount of food present. The findings are discussed in the context of Schachter's and Thomas and Mayer's explanations for human and VMH obesity.

Correlation between altered acetate utilization and hyperphagia in rats with ventromedial hypothalamic lesions

Incorporation of a tracer dose of acetate-1- 14C given by intraperitoneal injection into normal and VMH-lesioned rats 2 days after surgery has been studied in vivo. To exclude adaptive metabolic effects due to meal-feeding and hyperphagia, the food intake of the lesioned animals was kept close to normal by using an automated food dispenser. The results show decreased recovery of 14C activity as 14CO 2 in the lesioned rats as compared to untreated animals during the first 4 hr after the injection, whereas the 14C incorporation into body lipids was significantly increased in the lesioned animals. The change in acetate utilization is shown to develop gradually during the first 2–3 days postoperatively. Moreover, the individual retention of 14C activity from acetate-1- 14C is correlated to the subsequent gain in body weight during 8 days of ad-lib. feeding. In conclusion, the results clearly demonstrate an altered metabolism in the VMH-lesioned rat, so as to promote accumulation of body fat, even when hyperphagia is prevented. Furthermore, the concept “regulatory obesity” is reexamined in view of the findings presented.

The effects of pretraining on the bar-pressing performance of VMH-lesioned rats

Ventromedial hypothalamic lesioned rats preoperatively trained on an FR-128 schedule displayed postoperative improvements in performance which were a direct function of the degree of hyperphagia. The postoperative performance by the pretrained VMH-lesioned animals did not significantly differ from that of control animals during short test sessions following periods of deprivation, but substantially exceeded that of controls with continuous opportunity to respond. The increase in the number of pellets obtained was achieved by increases in both the meal size and the rate of bar-pressing. Previous attempts to account for the deficit in performance by nonpretrained VMH-lesioned animals in terms of decreased motivation or lowered activity are rejected in favor of an explanation based on a modification of affective response following such lesions.