Gb. Kaplan et al., REGULATION OF G PROTEIN-MEDIATED ADENYLYL-CYCLASE IN STRIATUM AND CORTEX OF OPIATE-DEPENDENT AND OPIATE WITHDRAWING MICE, Brain research, 788(1-2), 1998, pp. 104-110
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.