REGULATION OF G PROTEIN-MEDIATED ADENYLYL-CYCLASE IN STRIATUM AND CORTEX OF OPIATE-DEPENDENT AND OPIATE WITHDRAWING MICE

Previous research has demonstrated that acute and chronic opiate treat ment alters receptor-and postreceptor-mediated adenylyl cyclase activi ty. This study examined the regulation of G protein- and forskolin-med iated adenylyl cyclase activity in mouse striatum and cortex after sho rt- and long-term opiate exposure. To directly measure adenylyl cyclas e enzymatic activity, assays were done in the presence of catalytic si te activator forskolin. To measure G protein-mediated adenylyl cyclase activity, assays were performed in the presence of non-hydrolyzable g uanosine 5'-triphosphate (GTP) analogue, 5'-guanylyl-imidodiphosphate. Short-term in vitro morphine exposure produced reductions in forskoli n-stimulated adenylyl cyclase activity in striatal and cortical tissue s. Long-term morphine treatment in mice was performed via morphine- or placebo-pellet implantation for 72 h; this treatment has been shown t o produce opiate dependence and withdrawal. In both opiate-dependent a nd opiate withdrawing mice (1 h post-naloxone induction), there were s ignificant increases in G protein-mediated adenylyl cyclase activity i n the striatum (vs. controls). In opiate-dependent mice, there was an decrease in G protein-mediated adenylyl cyclase activity in cortex. In opiate-dependent mice, there were no changes in forskolin-stimulated adenylyl cyclase in the striatum or cortex. Increases in striatal G pr otein-mediated adenylyl cyclase could represent a compensatory adaptat ion that opposes the persistent inhibition of adenylyl cyclase by chro nic opiate treatment contributing to the expression of opiate dependen ce and withdrawal. (C) 1998 Elsevier Science B.V.