Disappearance of gamma-aminobutyric acid (GABA)B receptor-mediated cAMP suppression in mouse cerebrum after chronic treatment with morphine.
The effects of chronic morphine administration (dependence) and naloxone-induced withdrawal on cerebral GABAB receptor and its signal transduction system were examined. Alterations in receptor affinity and number and in the amount of Gi protein were determined by radioligand binding assay and immunoblotting with Gi protein antibody, respectively. [3H]GABA binding to GABAB receptors in the brain of morphine-dependent and -withdrawn mice showed no significant change in either high or low affinity sites. Similarly, no alterations were noted in the coupling between GABAB receptor and Gi protein or in the amount of protein. However, the suppressive effect of baclofen, a GABAB agonist, on forskolin-stimulated cAMP formation in cerebral cortical slices of these animals was abolished. These results indicate that chronic morphine administration may induce functional deterioration in the coupling between Gi protein and the adenylate cyclase system.
Ichida
T
T
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Kuriyama
K
K
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D018080:Receptors, GABA-B / Q000502:physiology*; D013375:Substance Withdrawal Syndrome
D018080:Receptors, GABA-B; D009020:Morphine; D000242:Cyclic AMP; D001418:Baclofen