Biomedical subjects

B A Gosnell

Publications and source records attributed to B A Gosnell.

At least 19 recordsLinked to original sources

PubMed1992

The effects of continuous naltrexone infusions on diet preferences are modulated by adaptation to the diets.

Two groups of male rats were placed on a feeding regimen in which a fat/protein diet and a carbohydrate/protein diet were available ad lib. Naltrexone was infused via osmotic minipumps either at the time the diets were introduced or after one week of adaptation to the diets. In rats adapted to the diets, naltrexone caused a decrease in the intakes of fat/protein and carbohydrate/protein diets. Relative preferences for the two diets were generally unchanged. In contrast, when naltrexone was infused at the time of introduction of the diets, a polarization phenomenon was observed: rats tended to consume nearly all of their daily calories from either one diet or the other. Six rats (out of 10) showed a stronger preference for the carbohydrate/protein diet than did any of the saline-treated rats, while 3 showed a stronger preference for the fat/protein diet than did any of the saline-treated rats. Thus, the effect was not diet- or macronutrient-specific. These preferences became significantly less extreme after termination of naltrexone infusions. Conditioned aversions and naltrexone-induced reductions in exploratory behavior are discussed as potential explanations for this polarization effect. These results indicate that naltrexone has differential effects on the development versus the maintenance of diet preferences. Further, they emphasize the importance of examining individual differences as well as baseline preferences in studies on the control of intake and diet selection.

Adaptation, Psychological↗

PubMed1992

Taste responses and preferences for sweet high-fat foods: evidence for opioid involvement.

Preferences and cravings for sweet high-fat foods observed among obese and bulimic patients may involve the endogenous opioid peptide system. The opioid antagonist naloxone, opioid agonist butorphanol, and saline placebo were administered by intravenous infusion to 14 female binge eaters and 12 normal-weight controls. Eight of the binge eaters were obese. During infusion, the subjects tasted 20 sugar/fat mixtures and were allowed to select and consume snack foods of varying sugar and fat content. Naloxone reduced taste preferences relative to baseline in both binge eaters and controls. Total caloric intake from snacks was significantly reduced by naloxone in binge eaters but not in controls. This reduction was most pronounced for sweet high-fat foods such as cookies or chocolate. No consistent effects on taste preferences or food intakes were observed with butorphanol. Endogenous opioid peptides may be involved in mediating taste responses and preferences for palatable foods, notably those rich in sugar and fat.

Adolescent↗

PubMed1991

Stealing in eating disordered patients.

Previous studies have noted high rates of stealing behavior in patients with eating disorders. To assess the significance of stealing in eating disordered patients, the authors compared the eating and purging behavior, levels of psychologic symptomatology, and alcohol use of 181 eating disordered patients with and without a history of stealing. Overall, the patients with a history of stealing had significantly more dysfunctional eating and purging behavior. Those patients with a history of stealing reported significantly more psychological distress including more depression, interpersonal sensitivity, obsessive compulsive behavior, and hostility. The authors conclude that stealing behavior should be assessed in patients with eating disorders as a history of stealing may define a subgroup of more severely impaired patients.

Adolescent↗

PubMed1990

The anorectic effects of CRH and restraint stress decrease with repeated exposures.

Intracerebroventricular (icv) administration of corticotropin-releasing hormone (CRH) or exposure to a restraint stressor causes acute anorexia in rats. However, the effects on food intake of repeated injections of CRH or repeated exposures to restraint stress have not been previously reported. As the effects of these more chronic CRH and stress treatments may be of greater relevance to emerging hypotheses of the pathogenesis of human eating and affective disorders, we measured the changes in food intake and body weight of rats after repeated central injections of CRH. In two experiments using two different daily dosages of CRH and two different schedules of administration, we found that the anorectic effect of CRH decreased over repeated injections. Weight gain was slowed significantly only in the high-dose experiment. Rats may become tolerant to the anorectic effects of CRH delivered by repeated icv injections. These findings have important implications for hypothesized mechanisms of anorexia nervosa and/or depression.

Animals↗

PubMed1990

Effects of a selective mu opioid receptor agonist and naloxone on the intake of sodium chloride solutions.

Endogenous opioid peptides are thought to play a role in mediating the palatability or rewarding aspects of sweet tastes. There is also evidence, however, which suggests that opioids may influence the preference for the taste of salt as well. In the present studies, we measured the effects of central administration of naloxone and the mu agonist [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO) on the ingestion of salt solutions. In non-deprived rats given a choice of water and 0.6% saline, ICV injections of DAGO (1 and 3 nmol) significantly increased the intake of 0.6% saline; baseline water intake was minimal and was unaffected by DAGO. When rats were given a choice between water and 1.7% saline, DAGO stimulated both water and saline intake. Because 1.7% saline is a hypertonic solution, the increase in water intake may have been secondary to saline intake. In rats on a deprivation schedule in which water and 0.6% saline were available for only 2-3 h/day, there was a tendency for DAGO to increase 0.6% saline intake and decrease water intake, though these effects were not significant. In rats given water and 1.7% saline, DAGO increased saline intake and had no effect on water intake. Naloxone was also tested in water-deprived rats. Naloxone (20 and 50 micrograms) significantly decreased 0.6% saline intake; baseline water intake was low (3-5 ml) and was unaffected by naloxone. When rats were given a choice between water and 1.7% saline, naloxone (50 micrograms) significantly reduced water intake, while intake of 1.7% saline was slightly increased. These results suggest a role for central mu opioid receptors in mediating the preference for salt solutions.

Animals↗

PubMed1990

Effects of preferential delta and kappa opioid receptor agonists on the intake of hypotonic saline.

A previous study has implicated central mu opioid receptors in the preference for salt solutions. Because mu, kappa and delta receptors are all thought to play a role in food intake and/or the mediation of palatability, we performed a series of experiments to determine whether preferential agonists at kappa and delta receptors might also stimulate the intake of salt solutions. When injected centrally into nondeprived rats, two selective agonists at delta receptors caused increases in the intake of 0.6% saline; the intake of concurrently available water was either unchanged or slightly increased. The selective kappa agonist U-50,488H had no effect on water or saline intake, whereas the preferential kappa agonist DAFPHEDYN caused a delayed increase in saline intake. These results indicate a role for central delta receptors in the preference for salt solutions, and are consistent with the suggestion that opioids play a role in the mediation of palatability.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1990

The effects of morphine on diet selection are dependent upon baseline diet preferences.

It has been reported that morphine causes a selective increase in the intake of dietary fat. Because we have noted considerable variability among rats in their preferences for carbohydrate and fat, we reasoned that the effect of morphine on diet selection may differ in fat-preferring vs. carbohydrate-preferring rats. Male Sprague-Dawley rats were given ad lib access to separate sources of carbohydrate, fat and protein (Experiment 1), or to a carbohydrate/protein and a fat/protein diet (Experiment 2). After daily baseline intakes of the diets were determined, all rats were tested for feeding responses to subcutaneous injections of morphine (0, 2 and 10 mg/kg). Significant positive correlations were found between baseline daily intake of a given diet and the effect of morphine on the intake of that diet. Generally, morphine increased carbohydrate intake in carbohydrate-preferring rats, and increased fat intake in fat-preferring rats. These results suggest that the effect of morphine is to increase intake of a preferred diet rather than to increase intake of a specific macronutrient.

Analysis of Variance↗

PubMed1989

Effects of streptozotocin-induced diabetes on feeding stimulated by centrally administered opioid agonists.

The potencies of several opioid agonists are reduced in diabetic animals and in animals made hyperglycemic via injections of glucose. In this report we examined the effects of streptozotocin-induced diabetes on the feeding responses to centrally administered opioid agonists with differing receptor selectivities. The selective mu receptor agonist Tyr-D-Ala-Gly-(Me)Phe-Gly-ol (DAGO) caused a larger increase in intake in diabetic rats than in controls. In both groups feeding responses were greater on the fourth day of daily injections than on the first day. The delta receptor agonist [D-Ser2,Leu5]-enkephalin-Thr6 (DSLET) stimulated intake in controls but not in diabetics. However, the elevated baseline and large variability in intake of the diabetics in this experiment prevent drawing a conclusion on diabetes-induced changes in the potency of this peptide. No differences between controls and diabetics were apparent in the feeding responses to U50, 488H, a selective kappa receptor agonist. These data suggest that diabetes may differentially affect the classes of opioid receptors or the binding of ligands to these receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1989

Centrally administered opioid peptides stimulate saccharin intake in nondeprived rats.

Endogenous opioid peptides are thought to play a role in mediating the pleasurable or rewarding aspects of the ingestion of certain foods and liquids. We therefore measured the effects of central administration of selective opioid agonists and naloxone on the intake of two concentrations of saccharin solution. All tests were performed on nondeprived rats, such that the taste of the solutions provided the primary incentive to consume. Intracerebroventricular (ICV) administration of the selective mu agonist [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO) and the selective delta agonist Tyr-D-Thr-Gly-Phe-Leu-Thr (DTLET) (3 nmol) increased intake of a 0.15% saccharin solution by approximately 10 ml over 3 hr. Water was available simultaneously, but intake was minimal. The selective kappa agonist U-50,488H did not increase intake of the saccharin solution. Naloxone (30 and 100 micrograms, ICV) caused a 44% reduction in saccharin solution intake in the first hour; two- and three-hour cumulative intakes were not different from control. DAGO and DTLET were also tested when rats were given a weaker saccharin solution (0.006%) along with water. Both agonists caused small increases in saccharin and water intake, but the increases above baseline were much smaller than those observed with the more palatable 0.15% saccharin solution. These results are consistent with reports by others which suggest that endogenous opioids influence taste preferences or palatability. Further, they indicate a role for central mu and delta opioid receptors in the mediation of this influence.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1989

Corticotropin-releasing hormone: possible role in eating disorders.

It has been hypothesized that corticotropin-releasing hormone (CRH) is an integral mediator in the pathophysiology of anorexia nervosa. This hypothesis is based on a) studies on patients with eating disorders which found elevated CRH levels in the cerebrospinal fluid and an abnormal response of the hypothalamopituitary (HYPAC) axis to intravenous CRH, and b) the discovery that the central administration of CRH to rats causes an acute anorectic state. Human and animal data supporting this hypothesis are reviewed, and important problems with the data base and the interpretation of these data are discussed. Appropriate directions for future research are highlighted.

Animals↗

PubMed1988

Behavioral effects of corticotropin-releasing factor: localization and characterization of central effects.

Corticotropin-releasing factor (CRF) has potent behavioral effects when administered intracerebroventricularly to rats. CRF and its receptors are found in an uneven distribution in the brain. In an effort to localize the site of the anorectic effect of CRF, exogenous CRF or saline was injected into cannulas directed toward the paraventricular hypothalamic nucleus (PVN), lateral hypothalamus, ventromedial hypothalamus, globus pallidus, or striatum of rats. CRF decreased food intake only when injected into the PVN. In subsequent experiments PVN injections of CRF were shown to (1) increase grooming and movement; (2) not induce a conditioned taste aversion to saccharin in a single bottle test; and (3) inhibit the increase in feeding induced by injections of norepinephrine into the PVN. These results suggest that CRF induces not only anorexia, but also increased movement and grooming by action in the PVN.

Animals↗

PubMed1988

Involvement of mu opioid receptors in the amygdala in the control of feeding.

The intake of food by rats was measured after unilateral injections of opioid peptides into or near the central nucleus of the amygdala. The selective mu receptor agonist Tyr-D-Ala-Gly-(Me)Phe-Gly-ol (DAGO) caused an increase in intake of food at doses of 1 and 3 nmol. Injections into the amygdala of [D-Ser2,Leu5]enkephalin-Thr6 (DSLET), a selective delta agonist, and dynorphin A, a selective kappa agonist, were ineffective at doses up to 3 nmol. However, dynorphin (2 nmol) did increase intake when injected into the medial hypothalamus. Bilateral injections of DAGO into the amygdala were no more effective than unilateral injections. The effect of DAGO was blocked by injections into the amygdala of naloxone or beta-chlornaltrexamine, an ultralong-lasting opioid receptor antagonist. These studies suggest that mu opioid receptors in the amygdala contribute to the regulation of intake of food. A role for kappa and delta receptors was not established but cannot be ruled out without further testing.

Amygdala↗

PubMed1988

Effect of morphine and nalmefene on energy balance in diabetic and non-diabetic rats.

Male rats made diabetic by intravenous injection of streptozotocin were used to evaluate the effect of the diabetic state on morphine- and nalmefene-induced changes in food intake and body weight. Morphine increased 4 hour food intake in non-diabetic rats after an initial injection, but increased intake in diabetic rats only after repeated injections. Unlike short term measurements, morphine decreased food intake when measured over 24 or more hours in both groups. Chronic injection of morphine decreased body weight only in non-diabetic rats. Feed efficiency data suggest that morphine had a more potent effect on energy balance in the non-diabetic rats. The opioid antagonist, nalmefene, did not alter body weight in either group and only altered food intake in the diabetic animals. These data are in concert with other reports indicating that the diabetic state renders animals less responsive to the effects of morphine on nociception and smooth muscle contraction.

Animals↗

PubMed1987

Effects of beta-chlornaltrexamine on food intake, body weight and opioid-induced feeding.

beta-Chlornaltrexamine (beta-CNA) is a non-equilibrium opioid receptor antagonist which alkylates and inactivates opioid receptors. Because opioid peptides are thought to contribute to the regulation of food intake, we examined the effects of intracerebroventricular (icv) injections of beta-CNA on the food intake and body weight of male rats. We also tested the ability of beta-CNA to block food intake stimulated by selective agonists of kappa, mu and delta opioid receptors: dynorphin A2 (DYN), Tyr-D-Ala-Gly-(Me)Phe-Gly-ol (DAGO), and [(D-Ser2,Leu5]-enkephalin-Thr6 (DSLET). Treatment with beta-CNA caused a long-term (2-4 days) reduction in daily food intake and a concomitant reduction in body weight. An additional experiment indicated that the weight loss after beta-CNA treatment could be completely accounted for by the reduction in intake. beta-CNA treatment also abolished or greatly attenuated the feeding effects of DAGO, DSLET and DYN, even when these peptides were tested 26 hours after beta-CNA administration. The long duration of the effects of beta-CNA suggests that this compound will be a useful pharmacological tool in further study of the opioid feeding system.

Animals↗

PubMed1987

Effects of dietary dehydroepiandrosterone on food intake and body weight in rats with medial hypothalamic knife cuts.

Dehydroepiandrosterone (DHEA) is a steroid which has been reported to have anti-obesity effects when added to the diets of rats and mice. In this report, rats made hyperphagic with medial hypothalamic knife cuts were placed on a diet containing 0.45% DHEA or a control diet. Knife cut rats on the control diet ate more food and gained more weight than sham-operated rats on the control diet. In contrast, knife cut rats fed the DHEA diet weighed the same as shams on the DHEA diet and were only observed to be hyperphagic on one of eight 24 hour measurements taken during a five week period. Dietary DHEA reduced food intake and body weight of both knife cut and sham-operated rats, though the effects were smaller in shams. As these effects of DHEA were reminiscent of the effects of dietary quinine adulteration on intake by knife cut rats, a second experiment measured the food intake of unoperated rats when given a choice between a control high-fat diet and one adulterated with various concentrations of DHEA. Even at a concentration of 0.05%, rats clearly identified and avoided the DHEA-adulterated diet. While these results do not rule out effects of DHEA on metabolic rate or lipogenesis, they do indicate that the unpalatability of DHEA-adulterated diets may be a contributing factor in the observed effects on food intake and body weight.

Animals↗

PubMed1987

Effects of kappa opiate agonists, cholecystokinin and bombesin on intake of diets varying in carbohydrate-to-fat ratio in rats.

Effects of the dietary carbohydrate-to-fat ratio on opiate-stimulated eating and on naloxone-, cholecystokinin- and bombesin-suppressed eating were examined. Rats were fed either a high carbohydrate (cornstarch) diet (68% of energy from carbohydrate and 12% from fat), an intermediate diet (40% carbohydrate and 40% fat) or a high fat (corn oil and lard) diet (3% carbohydrate and 77% fat). Other rats self-selected from the high carbohydrate and high fat diets. Subcutaneous administration of naloxone, an opiate antagonist, generally suppressed intake of the high fat diet to a greater extent than intake of the high carbohydrate diet. Neither cholecystokinin octapeptide nor bombesin (administered intraperitoneally) exerted preferential suppression of fat intake. The opiate agonists ketocyclazocine and butorphanol tartrate administered subcutaneously at 1000 h preferentially, although not exclusively, stimulated intake of the high fat diet in a dose-dependent manner during the 6-h feeding trial. Repeated daily subcutaneous injections of butorphanol tartrate caused rats to consume more than 50% of their daily intake during the 6-h period postinjection; intake during the normal night feeding period was suppressed to maintain total daily intake equal to that of vehicle-injected rats. We conclude that stimulation of the opioid feeding system contributes to the overeating often associated with consumption of a high fat diet.

Animals↗

PubMed1987

Effect of neuropeptide Y on ingestive behaviors in the rat.

Neuropeptide Y (NPY) is a potent stimulator of food and water intake in rats. NPY still increases food intake even after a 2-h delay in access to food after central injection. When two injections of NPY are given 2 h apart, the second injection produced a substantial increase in food intake. This suggests that tolerance to the NPY effect does not develop after a single injection of NPY. NPY increases moving and exploration in the absence of food when rats are in their home environment but not when tested in a novel environment. Following administration of NPY, rats preferred a high-carbohydrate diet over a high-fat or high-protein diet. Microinjections of NPY showed that active sites included the anterior ventromedial nucleus, paraventricular nucleus of the hypothalamus, and the posterior lateral hypothalamus. NPY was neither additive nor synergistic when coadministered with norepinephrine. Whereas norepinephrine-induced feeding was inhibited by adrenalectomy and vagotomy, these maneuvers had no effect on NPY-induced food intake. This provides further evidence that NPY does not exert its effects on food intake through an alpha-adrenergic mechanism. The effects of NPY on food intake were attenuated by peripherally administered bombesin and centrally administered corticotropin-releasing factor and calcitonin. Cholecystokinin failed to inhibit NPY-induced feeding. NPY did not alter circulating glucose levels. These studies provide further insights into the role of NPY as a stimulator of ingestive behaviors.

Adrenalectomy↗

PubMed1987

Central structures involved in opioid-induced feeding.

This paper summarizes efforts to identify structures involved in the opioid regulation of feeding. Many opioid agonists and antagonists increase or decrease food intake when injected centrally, which suggests, but alone does not prove, that the opioid feeding system is located within the brain. Some conditions of hunger and feeding cause changes in opioid peptide levels in certain brain areas, notably the hypothalamus, which may indicate that the areas are components of this opioid system. Lesion studies have also identified some potentially important structures, inasmuch as lesions of these structures reduce the effectiveness of opioid agonists or antagonists to alter food intake. Finally, microinjection studies have mapped the brain in terms of the effects on feeding of opioid agonists and antagonists. Results of different types of studies are consistent in suggesting that parts of the hypothalamus, particularly the paraventricular and ventromedial nuclei and the lateral hypothalamic area, are important components of the opioid feeding system.

Animals↗