Bruce M. King

Naloxone-induced suppression of food intake in normal and hypothalamic obese rats

Intraperitoneal injections of naloxone hydrochloride (1, 2, 4, and 8 mg/kg) suppressed food intake in both normal and hypothalamic obese rats maintained on a 4-hr per day feeding schedule. The decrease in feeding was more pronounced in the animals with ventromedial hypothalamic lesions. Appetitively motivated feeding, i.e., the consumption of sweetened milk under nondeprived conditions, was also suppressed by naloxone, but there was no reliable difference between groups. It is concluded that opiate receptors located in the ventromedial hypothalamus are not essential for the effects of opiate agonists and antagonists on feeding behavior.

Glucocorticoids and hypothalamic obesity

Recent studies have demonstrated a role for adrenal glucocorticoid hormones in the hyperphagia and obesity which follow lesions of the ventromedial hypothalamus (VMH). Although VMH lesions elevate morning plasma corticosterone levels, it is concluded that this contributes little to the development of obesity. More importantly, animals with VMH lesions appear to be hyperresponsive to very low levels of circulating glucocorticoids. The overeating and obesity are both prevented and reversed by either complete adrenalectomy or complete hypophysectomy (i.e., resulting in plasma corticosterone levels of less than 1.0 microgram/dl) and restored by dosages of glucocorticoids that have no effect on feeding behavior and weight gain in nonlesioned adrenalectomized animals. Mineralocorticoid hormones have no effect on hypothalamic obesity. Judging by the time course of effects on feeding behavior in VMH-damaged mice of a single intracerebroventricular injection of a low dose of glucocorticoid, which has no effect when administered intraperitoneally, it is concluded that glucocorticoids exert their effect centrally in a permissive, rather than a regulatory, manner. Stimulation of the neighboring paraventricular nuclei (PVN) with norepinephrine or neuropeptide Y produces a rapid feeding response which is also abolished by adrenalectomy and restored with administration of glucocorticoids. However, it is unlikely that the PVN is the site at which glucocorticoids exert their effect in animals with VMH lesions, for PVN lesions or knife-cuts, or combination VMH-PVN lesions, also result in hyperphagia and obesity. It is concluded that adrenal glucocorticoid hormones exert their permissive effects on feeding behavior at brain sites other than the medial hypothalamus. The septo-hippocampal complex is suggested as a possible site.

Effects of amygdala lesions on body weight, conditioned taste aversion, and neophobia

Female rats with posterodorsal amygdala (PDA), basolateral amygdala (BLA), or sham lesions were compared regarding ad libitum food intake, weight gain, consumption of a novel food, and acquisition of a conditioned taste aversion (CTA). While only the rats with PDA lesions evidenced substantial weight gains at 10 days after surgery eating standard lab chow (25-45 g more than the other groups), only the rats with BLA lesions demonstrated significant deficits in the CTA and neophobia paradigms. Rats with basolateral lesions, on average, took less than 30 s to begin drinking the novel sweetened condensed milk after pairing with illness while the other groups took approximately 15 min to begin drinking. Also, rats with basolateral lesions ate, on average, 5 g of the novel Froot Loops while the other groups ate approximately 2 g. It is concluded that the changes in food-motivated behavioral tests frequently observed in animals with amygdala lesions do not coexist with the hyperphagia and weight gain of animals with PDA lesions.

Comparison of Men's and Women's Attempts to Dissuade Sexual Partners From the Couple Using Condoms

Undergraduate students were asked about their use of condoms and their attempts to dissuade sexual partners from the couple using condoms during sexual intercourse. Nearly 14% of women and nearly 17% of men who had engaged in sexual intercourse admitted to having actively tried to dissuade a partner from the couple using condoms. Thirty percent of the men and 41% of the women said that a sexual partner had tried to dissuade them. Attempts to dissuade partners from the couple using condoms were most common among students who reported having 10 or more lifetime sexual partners. For both men and women, the most frequently employed categories of verbal strategies were (1) sex feels better without a condom, (2) will not get pregnant, and (3) will not get a sexually transmitted disease. These three categories accounted for about three-fourths of the lines used. Avoidance of condoms because of a perceived decrease in physical pleasure poses a particular problem for sex and health educators.

The role of vagally-mediated hyperinsulinemia in hypothalamic obesity

Evidence that the obesity syndrome which follows ventromedial hypothalamic (VMH) lesions is at least partially the result of a primary metabolic dysfunction is reviewed, as are proposals that the altered metabolism is due to enhanced vagally-mediated insulin release. This hypothesis was based largely on experiments demonstrating the complete reversal of hypothalamic obesity by subdiaphragmatic vagotomy, but subsequent studies have revealed that hypothalamic obesity is not always prevented by prior vagal transections. Interpretation of these discrepant results has been made difficult because of the frequent use of gastric secretion, behavioral, or other indirect tests for completeness of vagotomy. A review of more recent studies which have employed either direct assessment of vagotomy effects on insulin levels, pharmacological blockade of vagal efferent activity, or selective vagotomies indicates that vagally-mediated hyperinsulinemia can account for no more than 40% of the weight gain observed in animals with VMH lesions fed ad libitum, and may not be involved in the obesity that results from some parasagittal VMH knife cuts. It is concluded that vagally-mediated hyperinsulinemia does make a substantial, although not exclusive, contribution to the increased carcass lipid content observed in VMH animals that are food-restricted or pair-fed with control animals.

Amygdaloid-lesion hyperphagia: impaired response to caloric challenges and altered macronutrient selection

Lesions of the most posterodorsal aspects of the amygdala in female rats result in hyperphagia and moderate obesity. In the present study, rats with amygdaloid lesions did not increase their daily food intake when their powdered diet was diluted with 25 or 50% nonnutritive bulk. Control animals adjusted their food intake appropriately. In a second study, rats with lesions ate less food (lab chow pellets) than controls when allowed to eat for only 1 h/day for 10 days. In experiment 3, rats were offered a three-choice macronutrient diet. Whereas four of six control animals preferred the high-fat diet, all eight of the rats with amygdaloid lesions displayed a distinct preference for the high-carbohydrate diet, including those that had preferred the high-fat diet before surgery. These results, along with the previous finding that identical lesions result in hyperinsulinemia, indicate that the amygdala is involved in both the homeostatic regulation of food (caloric) intake and the selection of macronutrients.Lesions of the most posterodorsal aspects of the amygdala in female rats result in hyperphagia and moderate obesity. In the present study, rats with amygdaloid lesions did not increase their daily food intake when their powdered diet was diluted with 25 or 50% nonnutritive bulk. Control animals adjusted their food intake appropriately. In a second study, rats with lesions ate less food (lab chow pellets) than controls when allowed to eat for only 1 h/day for 10 days. In experiment 3, rats were offered a three-choice macronutrient diet. Whereas four of six control animals preferred the high-fat diet, all eight of the rats with amygdaloid lesions displayed a distinct preference for the high-carbohydrate diet, including those that had preferred the high-fat diet before surgery. These results, along with the previous finding that identical lesions result in hyperinsulinemia, indicate that the amygdala is involved in both the homeostatic regulation of food (caloric) intake and the selection of macronutrients.

Abnormal weight gain in rats with amygdaloid lesions

Marked weight gain was observed in female rats given small electrolytic lesions in the dorsal posterior portion of the amygdala. With a standard lab pellet diet, weight gains typically ranged between 20-30 g during the first 3 postoperative days, and between 60-100 g over the first 20 days. Rats with sham lesions generally gained only 5-15 g in 20 days. The results are consistent with much older studies that reported obesity in cats, dogs, and primates with lesions of the amygdala.

Sex differences in body weight gains following amygdaloid lesions in rats

Lesions of the most posterodorsal aspects of the amygdala resulted in equal weight gains (mean = 58 g) in male and female rats during a 22-day observation period. However, the absolute weight gains in the first 5 days after lesions were greater in females (+41.4 g) than in males (+18.8 g), as were the longer-term gains relative to their respective control groups. In a second study with female rats, it was found that amygdaloid lesions had little effect on the estrous cycle and that ovariectomy resulted in additional excessive weight gains in both rats with sham lesions and those with amygdaloid lesions. The weight gains produced by amygdaloid lesions and ovariectomy were additive. It is concluded that there is a sex difference in weight gains after amygdaloid lesions, but that the lesion-induced obesity is independent of estrogen levels. Similarities to lesions of the ventromedial hypothalamus are noted, and an amygdaloid-ventromedial hypothalamic pathway for the regulation of feeding behavior is proposed.Lesions of the most posterodorsal aspects of the amygdala resulted in equal weight gains (mean = 58 g) in male and female rats during a 22-day observation period. However, the absolute weight gains in the first 5 days after lesions were greater in females (+41.4 g) than in males (+18.8 g), as were the longer-term gains relative to their respective control groups. In a second study with female rats, it was found that amygdaloid lesions had little effect on the estrous cycle and that ovariectomy resulted in additional excessive weight gains in both rats with sham lesions and those with amygdaloid lesions. The weight gains produced by amygdaloid lesions and ovariectomy were additive. It is concluded that there is a sex difference in weight gains after amygdaloid lesions, but that the lesion-induced obesity is independent of estrogen levels. Similarities to lesions of the ventromedial hypothalamus are noted, and an amygdaloid-ventromedial hypothalamic pathway for the regulation of feeding behavior is proposed.

Effect on food intake and body weight of lesions in and adjacent to the posterodorsal amygdala in rats

Bilateral lesions centered in the posterodorsal amygdala of female rats resulted in hyperphagia and excessive weight gain. The brain damage extended posteriorly through the amygdalohippocampal area and into the ventral hippocampus and subiculum. Lesions centered in the ventral hippocampal formation had a less pronounced, although still significant, effect on body weight. Damage to large areas of the amygdala, including the anterior, basolateral, and corticomedial groups of nuclei, was without effect. A serial reconstruction of overlapping areas of destruction for both effective and ineffective lesions is presented.

Obesity-inducing lesions of the central nervous system alter leptin uptake by the blood-brain barrier

Leptin regulates body adiposity by decreasing feeding and increasing thermogenesis. Obese humans and some obese rodents are resistant to peripherally administered leptin, suggesting a defect in the transport of leptin across the blood-brain barrier (BBB). Defective transport of exogenous leptin occurs in some models of obesity, but in other models transport is normal. This shows that factors other than obesity are associated with impairment of leptin transport across the BBB. In order to further investigate these factors, we determined leptin transport in rats made obese by lesioning of the ventromedial hypothalamus (VMH), paraventricular nucleus (PVN), or posterodorsal amygdala (PDA). These regions all contain leptin receptors and lesions there induce obesity and hyperleptinemia and alter the levels of many feeding hormones which might participate in leptin transporter regulation. We measured the uptake of radioactively labeled leptin by the BBB by multiple-time regression analysis which divides uptake into a reversible phase (Vi, e.g., receptor/transporter binding to the brain endothelial cell) and an irreversible phase (Ki, complete transport across the BBB). Leptin uptake was not affected in rats with VMH lesions. No significant change occurred in the entry rate (Ki) for any group, although Ki declined by over 35% in rats with PVN lesions. Decreased uptake was observed in rats with PVN lesions and with PDA lesions. This was primarily due to a reduced Vi (about 21% for the PDA). This decreased uptake is most likely explained by decreased binding of leptin to the brain endothelial cell, which could be because of decreased binding by either receptors or transporters. This suggests that some of the feeding hormones controlled by the PVN and PDA may participate in regulating leptin uptake by the BBB.