Joel A. Grinker

Hypothalamic serotonin in the control of meal patterns and macronutrient selection

Serotonin (5-HT) is believed to have an inhibitory influence over feeding behavior. The present experiments were designed to investigate the effects of hypothalamic 5-HT on spontaneously motivated feeding and appetite regulation. Freely-feeding rats were injected with 5-HT or norfenfluramine (NORFENF) directly into the paraventricular hypothalamus (PVN), and precise changes in feeding behavior were monitored by a computer. Following PVN 5-HT or NORFENF injection, animals exhibited a marked suppression in food intake, associated with a decrease in meal size, duration and eating rate, and no change in the frequency of meals consumed. This suggests that brain 5-HT may influence primarily the induction of satiety rather than the suppression of hunger. The effect of drugs presumed to affect brain 5-HT transmission on diet selection was also investigated in groups of rats injected centrally with 5-HT or NORFENF or peripherally with either fenfluramine, quipazine or cyproheptadine. In a series of 2-diet tests, rats centrally injected with 5-HT or NORFENF exhibited a selective suppression of the carbohydrate-rich diets. In animals provided with three pure macronutrient diets, protein, carbohydrate, and fat, systemic administration of serotonergic agents had its greatest impact on fat and carbohydrate ingestion, as compared to protein consumption. These findings support a role for hypothalamic 5-HT in modulating meal patterns and appetite for particular macronutrients.

Contributions of age, sex and degree of fatness on preferences and magnitude estimations for sucrose in humans

Abstract Comparisons of magnitude estimate scaling for six suprathreshold concentrations (0.056–1.0 M) of sucrose by fifth graders, college students, and elderly persons revealed a steeper function for the children but no differences between the other two groups. Higher preferences were reported by males than by females for the sweeter concentrations and degree of fatness was inversely correlated with preference. These data suggest that deficits in sensory coding are not produced by old age and that important differences in sweet preference exist between human males and females.

Effects of d-amphetamine and fenfluramine on feeding patterns and activity of obese and lean Zucker rats

The effects of two doses of d-amphetamine and fenfluramine on male Zucker rats maintained ad lib on solid and liquid diets were investigated using the technique of meal pattern analysis. Amphetamine-induced anorexia was of short duration in both obese and lean rats. In the lean rats, anorexia was followed by rebound feeding resulting in little or no reduction in total daily intake. The drug reduced meal sizes of obese but not lean rats and caused a transient decrease in meal frequency. Increased spontaneous activity paralleled the decreased food intake. In contrast, anorexia following fenfluramine was greater, more prolonged and of equivalent magnitude in obese and in lean rats. No rebound feeding was observed. Reduction in intake was achieved primarily by changes in meal size rather than in meal frequency. These data demonstrate that food intakes of genetically obese Zucker rats are more susceptible to the action of d-amphetamine than those of lean rats, and are consistent with reports of differential neurotransmitter levels in the obese and lean rats.

Role of hypothalamic norepinephrine in control of meal patterns

Feeding behavior has been shown to be strongly affected by central administration of catecholamines. In this study, we examined in freely-feeding rats the effect of hypothalamic norepinephrine (NE) injections on the basic parameters of spontaneous ingestion. Precise changes in feeding behavior in rats maintained on ad lib food and water intake were monitored by a PDP 8 computer connected to an apparatus capable of measuring licks and bites of food. Injections of NE were administered into the hypothalamic paraventricular nucleus, the most sensitive brain area for the elicitation of feeding through direct alpha-noradrenergic stimulation. In tests conducted under both light and dark conditions, NE facilitated food intake, primarily by an increase in meal size rather than meal frequency. The first meal after injection was increased in size and duration; the rate of eating was also enhanced. Whereas the following intermeal interval was significantly larger, subsequent meals and intermeal intervals appeared generally unaffected. This evidence is consistent with the proposal of a role for hypothalamic NE in the maintenance, rather than initiation, of feeding behavior in freely-feeding rats.

Obesity and flavor perception: multidimensional scaling of soft drinks.

Multidimensional scaling procedures were used to assess the principal taste attributes of eight non-diet sodas as judged by obese and normal weight subjects. There were no systematic obese/normal differences either in flavor perception or in the reported patterns of taste preference. Hedonic ratings declined following repeated tasting of the sodas without swallowing. The decline in taste hedonics was greatest for the sodas perceived as sweetest, highest in calories and most intensely flavored, suggesting that changes in preference can be produced purely as a result of “flavor fatigue” and need not involve ingestion of calories.

The affective responses of obese patients to weight reduction: a differentiation based on age at onset of obesity.

&NA; The affective responses to weight reduction of five severely obese patients with adult onset of obesity were studied during a long‐term hospitalization. Anxious and depressive symptoms, measured by objective rating and self‐rating procedures, did not increase with weight loss. These results are in contrast to earlier findings from this laboratory of disturbances in affective responses following weight loss for patients with juvenile‐onset of obesity. These results suggest that the behavioral response to weight reduction is dependent upon age at onset of obesity.

Amphetamine: Effects on meal patterns and macronutrient selection

Catecholaminergic systems, specifically in the region of the lateral perifornical hypothalamus (PFH), have been linked to the inhibition of feeding behavior. The present studies examined the effects of d-amphetamine (AMPH), which is believed to act through the release of endogenous catecholamines (CAs), on spontaneous feeding and appetite regulation in rats. Injection of AMPH directly into the PFH caused a marked suppression of food intake; changes in computer-monitored meal patterns were characterized by an increase in the latency to meal onset and a consequent reduction in meal size and duration. This suggests that hypothalamic AMPH administration may influence primarily the initiation, rather than the termination, of feeding. In other experiments, chronic infusion of AMPH directly into the PFH was shown to suppress 24 hr food intake and body weight gain, indicating the effectiveness of lateral hypothalamic CA stimulation in overriding normal long-term patterns of feeding. The effect of hypothalamic CA stimulation on macronutrient selection was also investigated in groups of rats injected either centrally or peripherally with AMPH, or centrally with the CA agonists, dopamine and epinephrine. Each of these manipulations caused a strong inhibition of protein intake with no effect on carbohydrate, and only a mild suppression of fat ingestion after peripheral AMPH. These selective effects of AMPH on feeding patterns and diet choice, provide support for a role of CA innervation to the lateral hypothalamus in the modulation of natural feeding behavior and macronutrient selection.

Food and water intake, meal patterns and activity of obese and lean zucker rats following chronic and acute treatment with Δ9-tetrahydrocannabinol

Abstract A series of experiments investigated the effects of Δ 9 -THC on food and water intakes and wheel-running activity of Zucker rats. Following chronic drug treatment (15 days), food and water intakes of all rats were suppressed, but intakes and body weights of the obese rats recovered more slowly than those of lean rats. Acute effects of the drug (24 hr) were examined using techniques of meal pattern analysis and were discussed in relation to known patterns of anorectic drug action. The drug-induced anorexia was both delayed and of short duration, with no rebound eating observed for either solid or liquid diets. Both feeding rate and meal size were reduced, but meal frequency was transiently increased. The time of onset of the first meal remained unchanged. The time course of the suppression of feeding was paralleled by a suppression in running-wheel activity. These findings suggest that the drug-induced reduction in food and water intake may be the result of a decreased level of arousal.

Clonidine hyperphagia: Neuroanatomic substrates and specific function

Recent studies have indicated that the alpha 2-noradrenergic agonist clonidine (CLON), when peripherally and centrally administered, potentiates feeding in satiated rats in a manner similar to that observed following injection of norepinephrine (NE) into the hypothalamic paraventricular nucleus (PVN). The present experiments examined the effects of CLON on meal patterns and macronutrient selection and compared these findings to earlier NE-stimulated feeding studies. Administration of CLON (25 nmoles), directly into the PVN (n = 5), similar to PVN injected NE, produced an increase in meal size (190%) and feeding duration (164%), with no change in meal frequency. Additional tests were conducted in rats with PVN electrolytic or 6-hydroxydopamine lesions. In Sham rats (n = 16) peripheral CLON (0.05 mg/kg), like NE, produced an increase in food intake and particularly potentiated carbohydrate ingestion. Discrete electrolytic lesions of the PVN (n = 5) abolished this CLON-induced feeding and carbohydrate preference, suggesting that the PVN may be a primary site for CLON-stimulated hyperphagia. Neurotoxin lesions of the PVN (n = 17), which reduced PVN NE levels by 75%, failed to alter peripheral CLON-induced feeding. This and other evidence indicates that this agonist may be acting via postsynaptic alpha 2 receptors in the PVN to potentiate carbohydrate intake, rather than via presynaptic release of NE from nerve endings in the PVN.

The effect of the metabolite glycerol on food intake and body weight in rats

Abstract Plasma glycerol levels are correlated with adipose tissue mass and adipose cell size. Glycerol thus has been proposed as a humoral signal reflecting the state of fat storage. Small decrements in body weight and food intake following subcutaneous injections (2–4 daily) of glycerol have been reported. Oral administration of glycerol (1 g/kg/day) but not equicaloric glucose is effective in reducing body weight gain and decreasing food intake in growing male Sprague Dawley rats. Mature obese and lean Zucker male rats are similarly responsive to orally-administered glycerol at either 1 g/kg or 2 g/kg/day. Subcutaneous administration of 160 mg/kg/day of glycerol but not glucose via Alzet Mini-Pumps is also effective in reducing body weight gain and food intake. It thus appears unlikely that decreases in body weight gain or food intake following oral or peripheral glycerol administration are due to caloric or taste factors or to a primary osmotic diuretic effect. The observed glycerol effects in these experiments, however, are small and transient, with recovery beginning within 3–4 days of treatment. One possible interpretation of these data is that the action of exogenously administered glycerol is a function of the ratio of plasma glycerol to some other metabolite(s) which change with weight loss.