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 treatment alters receptor- and postreceptor-mediated adenylyl cyclase activity. This study examined the regulation of G protein- and forskolin-mediated adenylyl cyclase activity in mouse striatum and cortex after short- and long-term opiate exposure. To directly measure adenylyl cyclase enzymatic activity, assays were done in the presence of catalytic site activator forskolin. To measure G protein-mediated adenylyl cyclase activity, assays were performed in the presence of non-hydrolyzable guanosine 5'-triphosphate (GTP) analogue, 5'-guanylyl-imidodiphosphate. Short-term in vitro morphine exposure produced reductions in forskolin-stimulated adenylyl cyclase activity in striatal and cortical tissues. Long-term morphine treatment in mice was performed via morphine- or placebo-pellet implantation for 72 h; this treatment has been shown to produce opiate dependence and withdrawal. In both opiate-dependent and opiate withdrawing mice (1 h post-naloxone induction), there were significant increases in G protein-mediated adenylyl cyclase activity in 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 protein-mediated adenylyl cyclase could represent a compensatory adaptation that opposes the persistent inhibition of adenylyl cyclase by chronic opiate treatment contributing to the expression of opiate dependence and withdrawal.
Kaplan
G B
GB
Department of Psychiatry and Human Behavior, Veterans Affairs Medical Center and Brown University School of Medicine, Providence, RI 02908, USA.
Sethi
R K
RK
McClelland
E G
EG
Leite-Morris
K A
KA
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology*; D016015:Logistic Models; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000009:adverse effects*; D009021:Morphine Dependence / Q000201:enzymology*; D013375:Substance Withdrawal Syndrome; D013687:Telencephalon / Q000187:drug effects* / Q000201:enzymology
D005576:Colforsin; D009020:Morphine; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases