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 site for the mediation of unconditioned reinforcers such as food. Although both μ-selective and δ-selective opioid agonists in the NAcc induce spontaneous 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 μ ([D-Ala², NMe-Phe⁴, Gly-ol⁵]-enkephalin) or δ₂ ([D-Ala², Glu⁴]-deltorphin) opioid receptor subtype agonists in the shell region of the NAcc would be modified by intra-accumbens pretreatment with equimolar (12-100 nmol) doses of either D₁-selective (SCH23390) or D₂-selective (raclopride) antagonists. Both opioid agonists displayed comparable magnitudes and durations of feeding responses in the NAcc. SCH23390 significantly and dose-dependently reduced μ agonist-induced feeding in the NAcc with significant reductions noted following the two higher, but not two lower doses. In contrast, raclopride pretreatment produced inconsistent effects upon μ 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 δ₂ 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 (D₁ vs. D₂) as well as the opioid receptor subtype which was being stimulated (μ vs. δ₂). (C) 2000 Elsevier Science B.V.