Richard M. Gold

Paraventricular area: Critical focus of a longitudinal neurocircuitry mediating food intake☆

Abstract Hyperphagia, obesity, and excessive linear growth, but not hyperdipsia, were produced by the asymmetrical combination of a parasagittal hypothalamic knife cut and a contralateral coronal knife cut. When the location of the coronal cut was varied systematically, it was found that cuts rostral to the coronal level of the paraventricular nucleus (PVN) neither produced nor prevented overeating, while cuts caudal to the PVN produced a robust hyperphagic response. Thus, the coronal level of the paraventricular nucleus was revealed as the rostral focus of a longitudinal satiety neurocircuitry.

Circadian rhythms in vasopressin deficient rats

Circadian rhythms in wheel running and drinking behavior were investigated using heterozygous an homozygous (diabetes insipidus) female Brattleboro rats Despite the lack of vasopressin in the suprachiasmatic nuclei of the diabetic rats, they showed coherent rhythms, both in cyclic light and in constant light. However, the periods of the free-running rhythms were longer for the diabetic rats, they were less active, and, of course, were severely polydipsic. Replacement treatment with systemic infusions of vasopressin reversed the polydipsia but did not affect the other measures.

Differential effects of ovarian hormones on reactivity to electric footshock in the rat.

Abstract Flinch and jump thresholds in response to electric footshock were measured daily in estrous cycling female rats. Flinch thresholds fluctuated cyclicly with greatest sensitivity coinciding with periods of greatest estrogen activity. In ovariectomized animals estradiol benzoate increased flinch sensitivity while progesterone reduced it. In contrast, jump thresholds did not vary cyclicly in intact rats and were not influenced by estrogen or progesterone treatments in ovariectomized animals. These findings indicate that in female rats flinch thresholds are sensitive to ovarian hormone levels and that flinch and jump thresholds are independently modulated.

Effects of selective vagotomies on knife cut-induced hypothalamic obesity: Differential results on lab chow vs high-fat diets

Abstract Asymmetrical hypothalamic knife cuts were used to produce obesity in rats fed lab chow pellets. When the brain surgery was accompanied by selective section of the coeliac branch of the abomdinal vagus nerve, only 57% of the expected weight gain was observed. Additional section of the gastric branches of the vagus further reduced the knife cut effects, and complete subdiaphragmatic vagotomy suppressed body weight below control levels. Conversely, all vagotomies that spared the coeliac branch did not by themselves attenuate hypothalamic knife cut obesity. These results suggest that some function(s) under coeliac vagal control are specifically involved in mediating hypothalamic hyperphagia and obesity. When, after 30 days, the rats were switched to high-fat diet, all the knife cut rats overate and became obese (or more obese) irrespective of vagotomy status. This overeating despite vagotomy indicates that the vagus nerves must not be the exclusive mediator of hypothalamic obesity.

Hypothalamic Hyperphagia Despite Imposed Diurnal or Nocturnal Feeding and Drinking Rhythms

Rats normally do most of their eating at night. When ad lib fed rats are made hyperphagic with lesions or parasagittal hypothalamic knife cuts the increases in eating occur primarily during the day. This suggests that a disruption of circadian rhythms may mediate the overeating. However, when knife cut rats were food and water deprived all day excessive eating occurred at night. Similarly, when they were deprived all night overeating occurred during the day. Under both conditions od deprivation the food intakes and rapid weight gains of the ad lib fed knife cut group were defended. It was concluded that: (1) in hypothalamic hyperphagia either the excessive food intake or the excessive weight gain is defended when food and water are available only half of each day, and (2) disruption of nocturnal feeding and drinking rhythms is not the cause of hypothalamic hyperhagia.

Anodal electrolytic brain lesions: How current and electrode metal influence lesion size and hyperphagiosity ☆

Abstract Anodal electrolytic (DC) lesion were placed in the medial hypothalami of rats. With equal current parameters iron electrodes deposited more iron which produced larger lesions which produced greater weight gains than did stainless steel electrodes. Stainless steel electrode lesions were in turn larger and therefore more effective than equicoulombic lesions via platinum-iridium electrodes. Current delivered slowly via iron or steel electrodes produced larger lesions and as a result greater weight gains than did more rapid delivery of the same number of coulombs. Iron deposition appears to mediate iron and steel electrode lesions. Platinum electrode lesions seem to be mediated by oxygen bubbles and acidosis.

Effects of gastric vs complete subdiaphragmatic vagotomy on hypothalamic hyperphagia and obesity

Abstract Complete subdiaphragmatic vagotomy totally reversed pre-existing VMH lesion induced hyperphagia and obesity independent of the magnitude of the brain lesion effects, suggesting vagal participation in the VMH syndrome. However, complete vagotomy also reduced food and water intake and body weight in brain unlesioned controls. The specificity to VMH lesion obesity of the vagotomy effect is therefore questioned. Complete subdiaphragmatic vagotomy also reversed the obesity produced by prior hypothalamic knife cuts, and prevented the development of knife cut effects in rats which received knife cuts and vagotomies concurrently, or were permitted to recover from the acute effects of vagotomy before receiving knife cuts. Section of the gastric vagus, sparing the hepatic and coeliac branches, had no effect on knife cut-induced obesity, but did reduce water/food ratios and block increases in fasting gastric acid secretion. Thus, upper gastrointestinal effects cannot alone account for the blockade of obesity seen after complete vagotomy. This implicates the coeliac and/or hepatic vagal branches as important to the expression of hypothalamic obesity.

Ovariectomy-induced obesity is not prevented by subdiaphragmatic vagotomy in rats.

Abstract Bilateral subdiaphragmatic vagotomy did not prevent ovariectomy-induced obesity. Daily treatment with estradiol benzoate (2 μg/rat) reduced body weight in vagotomized rats to the same degree as in rats with intact vagi. Thus, neither ovariectomy-induced obesity nor the weight-suppressant action of estradiol depends on the vagus nerve.

Hypothalamic hypoactivity prevented but not reversed by subdiaphragmatic vagotomy

Abstract Parasagittal hypothalamic knife cuts produce a syndrome which includes obesity and hypoactivity. When the subdiaphragmatic vagi were cut at the same time as the brain cuts were made, both the obesity and the hypoactivity were prevented. This suggested that both the obesity and the hypoactivity are mediated by vagal hyperactivity. In contrast, however, when the subdiaphragmatic vagotomy was done 40–70 days subsequent to the brain cuts, the obesity was reversed, but the hypoactivity persisted. Thus, some aspect of the interoperative period irreversibly prevents the ability of vagotomy to reinstate normal activity levels in the rat.

The Lee Obesity Index vindicated

Correlations are reported for rats between the Lee Obesity Index and percent body fat. At weaning, rats were divided into 4 groups; supermarket diet and ovariectomy, supermarket diet and sham surgery. Lab Chow pellets and ovariectomy, and Lab Chow pellets and sham surgery. Four other groups received the treatments as adults. Eighteen and fifteen weeks later, respectively, the rats were measured for Obesity Index and were sacrificed for carcass analysis. The Obesity Index correlated well with percent body fat for animals made obese by diet; but it was not generally reliable for ovariectomized rats or for pellet fed sham operated controls. The Percent body fat also correlated well with body weight and with a simple weight/length ratio for rats made obese by diet. Thus, while the Obesity Index can reliably predict percent body fat, it may be no better at doing this than are some simpler measures.