CHANGES IN [H-3]FORSKOLIN BINDING TO ADENYLATE-CYCLASE AND [H-3]PHORBOL DIBUTYRATE BINDING TO PROTEIN-KINASE-C IN PENTOBARBITAL TOLERANT DEPENDENT RATS/

These studies were designed to examine the effect of chronic administr ation of pentobarbital on activity of adenylate cyclase (AC) and prote in kinase C (PKC) in the rat brain by autoradiography. Recently, it ha s been suggested that the phosphorylation of specific proteins may be involved in the development of physical dependence. An experimental mo del of barbiturate tolerance and dependence was developed using i.c.v. infusion of pentobarbital (300 mu g/ 10 mu l/hr for 7 days) by osmoti c minipumps and abrupt withdrawal from pentobarbital. The levels of [H -3]forskolin binding were elevated (28-67%) in cortex, thalamus, denta te gyrus, hippocampal CA3 and cerebellum of the pentobarbital withdraw al animals, while these changes were not observed in tolerant rats. Th e levels of [H-3]phorbol dibutyrate binding were highly elevated (38-6 5%) in the region of cortex, caudate putamen, septum, thalamus, dentat e gyrus, and cerebellum of rats withdrawal from pentobarbital. These r esults show that the levels of AC and PKC were significantly elevated in pentobarbital withdrawal rats, and suggest that the levels of AC an d PKC are altered in a region-specific manner during pentobarbital wit hdrawal.