Mercaptoacetate induces feeding through central opioid-mediated mechanismsin rats

The endogenous opioid system has been implicated in the mediation of food i ntake elicited by such regulatory challenges as glucoprivation induced by 2 -deoxy-D-glucose (2DG) or food deprivation in rodents. Administration of th e free fatty acid oxidation inhibitor, mercaptoacetate (MA), produces a pot ent short-term increase in feeding in rats, the mechanisms of which have be en dissociated from that elicited by 2DG. The present study evaluated wheth er MA-induced feeding in rats was mediated by the endogenous opioid system through systemic administration of the general opioid antagonist, naltrexon e, through central administration of either general, mu, mu(1), kappa(1) Or delta opioid antagonists, and through central administration of antisense oligodeoxynucleotide (AS ODN) probes directed against specific exons of eit her the mu (MOR-1), kappa (KOR-1), kappa(3) (KOR-3/ORL-1) or delta (DOR-1) opioid receptor clones. MA-induced feeding was significantly and dose-depen dently reduced by systemic naltrexone (0.005-5 mg/kg); these ingestive effe cts were quite selective since neither total, ambulatory nor stereotypic ac tivity was affected by either MA itself or MA paired with naltrexone. MA-in duced feeding was significantly reduced by central pretreatment with either naltrexone (0.1-20 mu g) or mu-selective (beta-funaltrexamine, 0.1-20 mu g ), mu(1)-selective (naloxonazine, 1-20 mu g), K-1-selective (nor-binaltorph amine, 0.1-20 mu g), or delta-selective (naltrindole, 1-20 mu g) opioid rec eptor antagonists. MA-induced feeding was significantly reduced by AS ODN p robes directed against either exons 1, 2 or 3, but not exon 3 of the MOR-1 clone, exon 3, but not exons 1 or 2 of the KOR-1 clone, exons 1 or 2, but n ot exon 3 of the KOR-3/ORL-1 clone, and exon 1, but not exons 2 or 3 of the DOR-I clone. These data are discussed in terms of opioid mediation of inge stive responses related to fat, and in terms of potential central sites of action at which lipoprivic ingestive responses might act. (C) 2000 Elsevier Science B.V. All rights reserved.