Evaluation of opioid receptor subtype antagonist effects in the ventral tegmental area upon food intake under deprivation, glucoprivic and palatable conditions

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 delta(1) ([D-Ala(2),Leu(5),Cys(6)]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, delta(1) or delta(2) (naltrindole isothiocyanate) opioid antagonists into the ventral tegmental area. Deprivation (24 h)-induced feeding was significantly reduced by high (50 mu g), but not lower(10-20 mu g) doses of naltrexone (21%), and by delta(2) (4 mu g, 19%) antagonism in the ventral tegmental area. 2-Deoxy-D-glucose (500 mg/kg, i.p.)-induced hyperphagia was significantly reduced by high (50 mu g), but not lower (20 mu g) doses of naltrexone (64%), and by delta(1) (4 mu g, 27%) antagonism in the ventral tegmental area. Sucrose (10%) intake was significantly reduced by naltrexone (20-50 mu g, 25-39%) and delta(2) (4 mu g, 25%) antagonism in the ventral tegmental area. Neither mu, kappa nor delta(1) 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 delta(2), rather than mu, kappa or delta(1) opioid receptors appear responsible for mediation of these forms of intake by this nucleus. (C) 1997 Elsevier Science B.V.