DIFFERENTIAL REGULATION OF ADENYLYL-CYCLASE ACTIVITY BY MU AND DELTA OPIOIDS IN RAT CAUDATE-PUTAMEN AND NUCLEUS-ACCUMBENS

The regulation of adenylyl cyclase by opioid receptor types was charac terized in the rat nucleus accumbens, a brain region that is involved in the reinforcing effects of drugs of abuse, and in the caudate putam en, a region not implicated in drug reinforcement. Both mu and delta o pioid ligands inhibited adenylyl cyclase activity in the nucleus accum bens and in the caudate putamen of rat, whereas the kappa agonist, U69 ,593 idinyl)-1-oxaspiro[4,5]dec-8-yl]-benzeneacetamide, was ineffectiv e. The mu agonists, DAMGO and Tyr-D-Arg-Phe-Sar, were more potent inhi bitors of the enzyme in caudate putamen than in nucleus accumbens. The delta-selective agonists, DSLET and [D-Ala2]-deltorphin II more poten tly inhibited adenylyl cyclase in nucleus accumbens than in caudate pu tamen. Inhibition of the enzyme by DAMGO and Tyr-D-Arg-Phe-Sar was ant agonized by the mu-selective competitive antagonist, CTOP D-Phe-Cys-Ty r-D-Trp-Orn-Thr-Pen-Thr-NH2, and the noncompetitive mu antagonists, be ta-funaltrexamine and naloxonazine. Inhibition of adenylyl cyclase act ivity by the delta-selective ligands, DPDPE, DSLET and [D-Ala2]-deltor phin II was unaffected by these antagonists. Conversely, the de/ta-sel ective antagonists, ICI 174,864 N-allyl2-Tyr-(alpha-aminisobutyric aci d)2-Phe-Leu-OH and naltrindole, blocked the effects of the delta but n ot the mu opioid ligands. Adenylyl cyclase activity in nucleus accumbe ns and in caudate putamen is subject to regulation by both mu and delt a opioid receptors.