norbinaltorphimine and Hyperphagia

The obese Zucker rat (OZR) exhibits a hyperphagic eating pattern similar to the obese binge eater. Dynorphin, an endogenous agonist of the kappa receptor, is associated with regulation offood intake. Lessened sensitivity to opioid antagonists and/or increased central dynorphin levels may contribute to the hyperphagic eating pattern observed in the OZR. This study examined the temporal effect of a single intracerebroventricular (ICV) dose of nor-binaltorphimine (NBNI), a specific and long-lasting kappa opioid antagonist, on food intake, body weight, and satiety measures (meal size and the shape of the cumulative food intake curve [CFIC]) in adult male OZRs. Analysis of individual subjects revealed a differential response to opioid antagonism with respect to weight loss, reduction in food intake, and change in the slope of the CFIC, with some responding and others responding poorly. Repeated-measures analysis of variance showed a significant decrease in body weight (P = 0.001) and food intake (P = 0.03) in responders compared to poor responders and controls. Satiation was influenced to a greater extent in responders, who showed a significant reduction in meal size and a greater change in the CFICfor the largest meal of the day toward a pattern of satiation. These data suggest that a differential response to chronic opioid antagonism may exist in the OZR.

Topics: Animals; Body Weight; Brain; Bulimia; Energy Intake; Feeding Behavior; Hyperphagia; Injections, Intraventricular; Models, Animal; Naltrexone; Narcotic Antagonists; Obesity; Rats; Rats, Zucker; Satiation

Opioid receptor subtype antagonists differentially alter food intake under deprivation (24 h), glucoprivic (2-deoxy-D-glucose, 500 mg/kg, i.p.) or palatable (10% sucrose) conditions with mu (beta-funaltrexamine) and kappa (nor-binaltorphamine), but not delta1 ([D-Ala2,Leu5,Cys6]enkephalin) opioid antagonists reducing each form of intake following ventricular microinjection. Both mu and kappa opioid antagonists microinjected into either the hypothalamic paraventricular nucleus or the nucleus accumbens reduce intake under deprivation and glucoprivic conditions. Palatable intake is reduced by both antagonists in the paraventricular nucleus, but only mu antagonists are active in the accumbens. Food intake is stimulated by mu and delta, but not kappa, opioid agonists microinjected into the ventral tegmental area. The present study examined whether food intake under either deprivation, glucoprivic or palatable conditions was altered by bilateral administration of general (naltrexone), mu, kappa, delta1 or delta2 (naltrindole isothiocyanate) opioid antagonists into the ventral tegmental area. Deprivation (24 h)-induced feeding was significantly reduced by high (50 microg), but not lower (10-20 microg) doses of naltrexone (21%), and by delta2 (4 microg, 19%) antagonism in the ventral tegmental area. 2-Deoxy-D-glucose (500 mg/kg, i.p.)-induced hyperphagia was significantly reduced by high (50 microg), but not lower (20 microg) doses of naltrexone (64%), and by delta2 (4 microg, 27%) antagonism in the ventral tegmental area. Sucrose (10%) intake was significantly reduced by naltrexone (20-50 microg, 25-39%) and delta2 (4 microg, 25%) antagonism in the ventral tegmental area. Neither mu, kappa nor delta1 antagonists were effective in reducing any form of intake following microinjection into the ventral tegmental area. These data indicate that the ventral tegmental area plays a relatively minor role in the elicitation of these forms of food intake, and that delta2, rather than mu, kappa or delta1 opioid receptors appear responsible for mediation of these forms of intake by this nucleus.

Topics: Deoxyglucose; Eating; Enkephalin, Leucine-2-Alanine; Evaluation Studies as Topic; Food Deprivation; Hyperphagia; Insulin; Naltrexone; Narcotic Antagonists; Sucrose; Ventral Tegmental Area