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Biomedical subjects

B G Stanley

Publications and source records attributed to B G Stanley.

43 records · Page 3Linked to original sources

Neurotensin: effects of hypothalamic and intravenous injections on eating and drinking in rats.

To investigate a role for the brain-gut peptide neurotensin (NT) in ingestive behavior, changes in food and water intake of food-deprived rats were examined following injection of NT into the paraventricular hypothalamic nucleus (PVN) or the mesenteric vein. Unilateral PVN NT (2.5, 5.0, 10.0 micrograms/0.3 microliter) produced substantial dose-dependent reductions in total food intake 0.5, 1, and 4 hr postinjection. In contrast, PVN NT had no effect on water intake and produced no change in grooming, rearing, sleeping, resting or locomotor activity. Bilateral PVN NT at a high dose (10.0 micrograms/side) suppressed consumption of solid or liquid diet in food-deprived rats, but did not affect water intake in water-deprived rats. This specificity is consistent with a role for CNS NT in feeding behavior. Intravenous NT (1-1000 pmole/kg/min for 30 min) did not specifically suppress food intake; however, low doses did increase water intake in food-deprived rats. These findings do not support a role for plasma NT in feeding, but do suggest that it may play a role in drinking behavior.

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Paraventricular nucleus injections of peptide YY and neuropeptide Y preferentially enhance carbohydrate ingestion.

Neuropeptide Y (NPY) injected into the paraventricular nucleus (PVN) is known to elicit a powerful feeding response in satiated, brain-cannulated rats. The present experiment investigates the effect of peptide YY (PYY), a structurally-related peptide, on feeding behavior and, in addition, the effects of both PYY and NPY on the pattern of macronutrient selection. Injection of PYY directly into the PVN, in doses ranging from 7.8 to 235 pmol/0.3 microliters, caused a strong, dose-dependent stimulation of feeding behavior, as well as a small stimulation of drinking behavior, in satiated rats. The mean latency to eat was 9.3 min, with substantial feeding occurring within 30 min of the injection. At low doses, the increase in feeding was seen predominantly during the first hr. At the highest dose, in contrast, food intake continued to increase progressively over the next few hr. such that by 4 hr postinjection food intake was more than 20 g over vehicle baseline. In 1 hr tests with 3 pure macronutrient (protein, fat and carbohydrate) diets simultaneously available, PYY and NPY (78 pmol/0.3 microliters) both elicited a strong and selective increase in carbohydrate consumption, with little or no effect on protein or fat consumption. These results suggest that hypothalamic receptors sensitive to PYY and NPY may participate in the control of carbohydrate consumption.

Animals↗

Neuropeptide Y chronically injected into the hypothalamus: a powerful neurochemical inducer of hyperphagia and obesity.

Neuropeptide Y (NPY), a putative neurotransmitter abundant in the brain, has recently been shown to act within the hypothalamus, inducing a powerful eating response and a specific appetite for carbohydrates. In the present study, NPY (235 pmol) injected bilaterally in the paraventricular nucleus three times a day for 10 days caused approximately a two-fold increase in daily food intake, a six-fold increase in the rate of body weight gain and a three-fold increase in the body fat of female rats. Subsequently, the food intake and body weight of these subjects decreased precipitously, reaching control levels 20 days postinjection. These findings, demonstrating that exogenous NPY is capable of overriding mechanisms of satiety and body weight control, suggest that disturbances in NPY function may play a role in some disorders of eating behavior and body weight regulation.

Adipose Tissue↗

Bombesin-induced anorexia: sites of action in the rat brain.

To determine the brain sites at which centrally injected bombesin (BBS) may act to suppress feeding behavior, this peptide (1.0 micrograms/0.3 microliter) was microinjected into one of twelve brain regions in 6 hr food deprived rats, and food intake was measured 45 min postinjection. Bombesin produced its strongest suppression of feeding (47-65%) when injected into hypothalamic areas, namely, the paraventricular, dorsomedial, ventromedial nuclei and lateral hypothalamus, and also when administered into the amygdala and the periaqueductal gray. Insensitive areas included the septum, ventral tegmental area and reticular formation. In contrast to these somewhat site-specific effects on feeding behavior, observation of BBS' effects on other behaviors revealed that, in all brain areas tested, there was a significant increase in grooming behavior and decrease in time spent resting and sleeping. In conjunction with high levels of BBS-like immunoreactivity and BBS receptors in the brain areas where injected BBS suppresses feeding, these results suggest that the effects of centrally administered BBS on feeding behavior may be mediated by multiple hypothalamic and extra-hypothalamic brain regions.

Animals↗

Stimulation of feeding by galanin: anatomical localization and behavioral specificity of this peptide's effects in the brain.

The neuropeptide galanin (GAL) has been found to elicit eating after injection into the hypothalamic paraventricular nucleus (PVN). To determine whether GAL's effect in the brain is anatomically specific, this peptide (0.1 or 0.3 nmol) was microinjected into one of 14 different brain areas of rats, and its impact on subsequent food intake was measured. Among the hypothalamic sites tested, only the PVN and the adjacent periventricular region yielded a significant eating response to GAL. With injection into the PVN, a feeding response was observed without apparent changes in other food-associated behaviors, e.g., drinking, grooming, resting and sleeping, or low and high levels of activity. All other hypothalamic and extrahypothalamic sites tested were unresponsive to GAL, with the exception of the amygdala where a significant eating response was observed. These findings suggest that central GAL elicits feeding by acting in an anatomically localized and behaviorally specific manner. In light of other pharmacological and anatomical evidence, it is suggested the PVN GAL, in modulating feeding behavior, may work in association with the catecholamine norepinephrine (NE) which is known to coexist with GAL in PVN neurons.

Animals↗

Evidence for neuropeptide Y mediation of eating produced by food deprivation and for a variant of the Y1 receptor mediating this peptide's effect.

Neuropeptide Y (NPY) elicits eating when injected directly into the paraventricular nucleus (PVN) or perifornical hypothalamus (PFH). To identify the essential regions of the NPY molecule and the relative contributions of Y1 and Y2 receptors, the eating stimulatory potency of NPY was compared to that of its fragments, analogues, and agonists when injected into the PVN or PFH of satiated rats. Additionally, antisera to NPY was injected into the cerebral ventricles (ICV) to determine whether passive immunization suppresses the eating produced by mild food deprivation. Tests with NPY fragments revealed that NPY(2-36) was surprisingly potent, nearly three times more so than intact NPY. In contrast, fragments with further N-terminal deletions were progressively less effective or ineffective, as was the free acid form of NPY. Collectively, this suggests that both N- and C-terminal regions of NPY participate in the stimulation of eating. Tests with agonists revealed that the putative Y1 agonist [Pro34]NPY elicited a strong dose-dependent feeding response, while the putative Y2 agonist, C2-NPY, had only a small effect at the highest doses. Although this suggests mediation by Y1 receptors, the uncharacteristically high potency of NPY(2-36) may additionally suggest that the receptor subtype underlying feeding is distinct from that mediating other responses. Additional results revealed that ICV injection of antisera to NPY, which should inactivate endogenous NPY, produced a concentration-dependent suppression of eating induced by mild food deprivation. This finding, along with published work demonstrating enhanced levels of hypothalamic NPY in food-deprived rats, suggests that endogenous NPY mediates the eating produced by deprivation.

Amino Acid Sequence↗

Feeding responses to perifornical hypothalamic injection of neuropeptide Y in relation to circadian rhythms of eating behavior.

Hypothalamic injection of neuropeptide Y (NPY) can elicit eating in satiated rats, and the perifornical hypothalamus (PFH) is the site where this effect is most pronounced (48). Additionally, there is a well-documented circadian rhythm of spontaneous eating behavior. Our objective was to determine whether there are daily rhythms of sensitivity to NPY in the PFH that might contribute to this behavioral rhythm. To accomplish this, the effectiveness in eliciting eating of PFH injection of NPY was examined at six different time points in the light-dark cycle. Neuropeptide Y (78 pmol/10 nl) or vehicle (10 nl) were injected through chronically implanted guide cannulas into the PFH of satiated adult male rats and food intake was measured 1, 2, and 4 h later. In animals on 12-12 h light-dark cycles, these injections were given 1 h before and after the onset of the light and dark phases, and in the middle of these phases. Additionally, dose-response effects of NPY were examined at two points: the first hour of both the dark and the light phases. The results show that NPY was effective at every time tested, and that the magnitude of the peptide-elicited intakes was primarily additive to the underlying patterns of spontaneous intake, with only a modest daily cycle of sensitivity to NPY. Consistent with this, NPY dose-dependently increased intake in the early light and in the early dark, and the magnitude of these effects across doses was similar at these times. This suggests that the sensitivity of the PFH system mediating NPY eating exhibits only a modest daily cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

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