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Biomedical subjects

J A Grinker

Publications and source records attributed to J A Grinker.

11 recordsLinked to original sources

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.

Animals

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.

Animals

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.

Animals

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.

Animals

Effects of inhibitors of carbohydrate absorption or lipid metabolism on meal patterns of Zucker rats.

Peripherally active anorectic agents represent a new approach to the pharmacological management of obesity. Two inhibitors of carbohydrate absorption: an alpha-glucosidase inhibitor, acarbose (Bay g 5421) and a alpha-amylase inhibitor, Ro 12-2272, were compared with two novel inhibitors of lipid metabolism: an inhibitor of human pancreatic lipase (Ro 20-0083) and of hepatic fatty acid synthesis (Ro 22-0654). All drugs were presented as diet admixtures over 3 or 4 consecutive days. Total food and water intakes, the temporal pattern of feeding, and the average meal frequency and meal size were measured using computerized data collection procedures. Inhibitors of carbohydrate absorption failed to suppress food intake in either obese or lean Zucker rats and had no effect on the parameters of feeding. In contrast, inhibitors of lipid metabolism reduced food intake by 56-77% by reducing both meal frequency and meal size. Direct inhibition of lipid metabolism may be a viable mechanism for anti-obesity agents.

Acarbose

Food and water intake, meal patterns and activity of obese and lean Zucker rats following chronic and acute treatment with delta9-tetrahydrocannabinol.

A series of experiments investigated the effects of delta9-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.

Animals

Sensory responses, dietary-induced obesity and biochemical values in Sprague-Dawley rats.

Food intake and body weight gain variability in Sprague-Dawley (SD) rats exposed to a palatable high-fat diet were examined in relation to sensory responses and biochemical parameters in two experiments. In the first experiment, varying sucrose concentrations (4-32% wt./vol.) were randomly presented for 20 minutes to ad lib chow-fed rats. Each rat's sensory response was expressed as Beta (B), or the slope of the regression between solute intake and concentration, and used to assign rats to diet groups. In the second experiment, responsiveness to fat emulsions (1-37%) were similarly measured and categorized. In both experiments sensory responses to sucrose were significantly related to weight gain/fatness on the high-fat diet (lab chow-corn oil). Sensory responsiveness to the fat emulsions was unrelated to sucrose responsiveness or to high-fat feeding. Biochemical parameters (insulin, cholesterol, triglycerides, lipoproteins) reflected increased caloric (fat) intake, as well as sucrose responsiveness. Predictors (sensory responses, biochemical values) of response to chronic (4 months) or short-term (less than 2 months) high-fat diets are discussed.

Adipose Tissue

Body composition, body size estimation, and attitudes towards eating in male college athletes.

A number of different parameters relating to eating history and body composition were examined in male college athletes during the course of an athletic season. Wrestlers, who often lose weight to meet the requirements of the sport, were compared with other athletes (swimmers, nordic skiers) who typically maintain weight during vigorous training. By the end of the athletic season, the wrestlers had reduced body weights and reported a reduction in caloric intakes. Wrestlers scored higher than swimmers and nordic skiers on scales measuring dietary restraint and attitudes towards eating (EAT). The groups differed primarily on items dealing with fluctuations in body weight and with dieting behaviors. There were no significant differences between groups on the estimates of body size and no effect of seasonal training. However, a small subsample of the wrestlers who scored high on the restraint and EAT scales also showed distortions in estimates of body size. Wrestlers may represent a population at risk for the newly reported sports-induced disturbances in eating.

Adolescent