gamma-Aminobutyric acid receptor subtype antagonists differentially alter opioid-induced feeding in the shell region of the nucleus accumbens in rats

Food intake is significantly increased by administration of mu -selective o pioid agonists into the nucleus accumbens, particularly its shell region. P retreatment with either opioid (mu, delta (1), delta (2) or kappa (1)) or d opaminergic (D-1) receptor antagonists in the nucleus accumbens shell reduc e mu opioid agonist-induced feeding. Selective GABA(A) (muscimol) and GABA( B) (baclofen) agonists administered into the nucleus accumbens shell each s timulate feeding which is respectively and selectively blocked by GABA(A) ( bicuculline) and GABA(B) (saclofen) antagonists. The present study investig ated whether feeding elicited by the mu -selective opioid agonist, [D-Ala(2 ),NMe4,Gly-ol(5)]-enkephalin in the nucleus accumbens shell was decreased b y intra-accumbens pretreatment with an equimolar dose range of either GABA or GABA(B) antagonists, and further, whether general opioid or selective GA BA antagonists decreased feeding elicited by GABA(A) or GABA(B) agonists in the nucleus accumbens shell. Feeding elicited by the mu -selective opioid agonist was dose-dependently increased following intra-accumbens pretreatme nt with GABA(A) (bicuculline) antagonism: this enhancement was significantl y blocked by pretreatment with general or mu -selective opioid antagonists. In contrast, mu opioid agonist-induced feeding elicited from the nucleus a ccumbens shell was dose-dependently decreased by GABA(B) (saclofen) antagon ism. Neither bicuculline nor saclofen in the nucleus accumbens shell altere d baseline food intake. Whereas muscimol-induced feeding elicited from the nucleus accumbens shell was reduced by bicuculline and naltrexone. but not saclofen pretreatment. baclofen-induced feeding elicited from the nucleus a ccumbens shell was reduced by saclofen, but not by bicuculline or naltrexon e. These data indicate that GABA(A) and GABA(B) receptor subtype antagonist s differentially affect feeding elicited by mu opioid receptor agonists wit hin the nucleus accumbens shell in rats. (C) 2001 Elsevier Science B.V. All rights reserved.