The effects of intranigral injection of substance P, d-ala 2-metenkephalinamide and muscimol on the perioal biting reflex

Abstract

Food intake is significantly increased by administration of μ-selective opioid agonists into the nucleus accumbens, particularly its shell region. Pretreatment with either opioid (μ, δ1, δ2 or κ1) or dopaminergic (D1) receptor antagonists in the nucleus accumbens shell reduce μ opioid agonist-induced feeding. Selective GABAA (muscimol) and GABAB (baclofen) agonists administered into the nucleus accumbens shell each stimulate feeding which is respectively and selectively blocked by GABAA (bicuculline) and GABAB (saclofen) antagonists. The present study investigated whether feeding elicited by the μ-selective opioid agonist, [d-Ala2,NMe4,Gly-ol5]-enkephalin in the nucleus accumbens shell was decreased by intra-accumbens pretreatment with an equimolar dose range of either GABAA or GABAB antagonists, and further, whether general opioid or selective GABA antagonists decreased feeding elicited by GABAA or GABAB agonists in the nucleus accumbens shell. Feeding elicited by the μ-selective opioid agonist was dose-dependently increased following intra-accumbens pretreatment with GABAA (bicuculline) antagonism; this enhancement was significantly blocked by pretreatment with general or μ-selective opioid antagonists. In contrast, μ opioid agonist-induced feeding elicited from the nucleus accumbens shell was dose-dependently decreased by GABAB (saclofen) antagonism. Neither bicuculline nor saclofen in the nucleus accumbens shell altered 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 accumbens shell was reduced by saclofen, but not by bicuculline or naltrexone. These data indicate that GABAA and GABAB receptor subtype antagonists differentially affect feeding elicited by μ opioid receptor agonists within the nucleus accumbens shell in rats.