Multiple opioid receptors mediate feeding elicited by mu and delta opioid receptor subtype agonists in the nucleus accumbens shell in rats

The nucleus accumbens, and particularly its shell region, is a critical site at which feeding responses can be elicited following direct administration of opiate drugs as well as micro-selective and delta-selective, but not kappa-selective opioid receptor subtype agonists. In contrast to observations of selective and receptor-specific opioid antagonist effects upon corresponding agonist-induced actions in analgesic studies, ventricular administration of opioid receptor subtype antagonists blocks feeding induced by multiple opioid receptor subtype agonists. The present study examined whether feeding responses elicited by either putative mu (D-Ala(2), NMe-Phe(4), Gly-ol(5)]-enkephalin (DAMGO)), delta(1) (D-Pen(2), D-Pen(5)]-enkephalin (DPDPE)) or delta(2) (D-Ala(2), Glu(4)]-deltorphin (Deltorphin)) opioid receptor subtype agonists administered into the nucleus accumbens shell were altered by accumbens pretreatment with either selective mu (beta-funaltrexamine), mu(1) (naloxonazine), delta(1) (D-Ala(2), Leu(5), Cys(6)]-enkephalin (DALCE)), delta(2) (naltrindole isothiocyanate) or kappa(1) (nor-binaltorphamine) opioid receptor subtype antagonists. Similar magnitudes and durations of feeding responses were elicited by bilateral accumbens administration of either DAMGO (2.5 microg), DPDPE (5 microg) or Deltorphin (5 microg). DAMGO-induced feeding in the nucleus accumbens shell was significantly reduced by accumbens pretreatment of mu, delta(1), delta(2) and kappa(1), but not mu(1) opioid receptor subtype antagonists. DPDPE-induced feeding in the accumbens was significantly reduced by accumbens pretreatment of mu, delta(1), delta(2) and kappa(1), but not mu(1) opioid receptor subtype antagonists. Deltorphin-induced feeding in the accumbens was largely unaffected by accumbens delta(2) antagonist pretreatment, and was significantly enhanced by accumbens mu or kappa(1) antagonist pretreatment. These data indicate different opioid pharmacological profiles for feeding induced by putative mu, delta(1) and delta(2) opioid agonists in the nucleus accumbens shell, as well as the participation of multiple opioid receptor subtypes in the elicitation and maintenance of feeding by these agonists in the nucleus accumbens shell.