Analysis of dopamine receptor antagonism upon feeding elicited by mu and delta opioid agonists in the shell region of the nucleus accumbens

The nucleus accumbens (NAcc) has been implicated as an important reward sit e for the mediation of unconditioned reinforcers such as food. Although bot h mu-selective and delta-selective opioid agonists in the NAcc induce spont aneous and palatable feeding, these effects are mediated by multiple opioid receptor subtypes within the nucleus. A role for dopaminergic mediation of feeding in the NAcc is based upon selective antagonist-induced suppression of feeding induced by systemic amphetamine. The present study investigated whether feeding elicited by infusion of either mu ([D-Ala(2), NMe-Phe(4), Gly-ol(5)]-enkephalin) or delta(2) ([D-Ala(2), Glu(4)]-deltorphin) opioid r eceptor subtype agonists in the shell region of the NAcc would be modified by intra-accumbens pretreatment with equimolar (12-100 nmol) doses of eithe r D-1-selective (SCH23390) or D-2-selective (raclopride) antagonists. Both opioid agonists displayed comparable magnitudes and durations of feeding re sponses in the NAcc. SCH23390 significantly and dose-dependently reduced mu agonist-induced feeding in the NAcc with significant reductions noted foll owing the two higher, but not two lower doses. In contrast, raclopride pret reatment produced inconsistent effects upon mu agonist-induced feeding with limited actions across doses and test times. Further, neither SCH23390 nor raclopride pretreatment in the NAcc affected feeding elicited by the delta (2) opioid agonist. These data indicate that the role of dopamine receptors in mediating opioid-induced feeding within the shell region of the NAcc is both dependent upon the dopamine receptor subtype that was blocked (D-1 vs . D-2) as well as the opioid receptor subtype which was bring stimulated (m u vs. delta(2)). (C) 2000 Elsevier Science B.V. All rights reserved.