Ethanol exposure alters the phosphorylation of cyclic AMP responsive element binding protein and cyclic AMP responsive element binding activity in rat cerebellum

The purpose of the present study was to track the acute effects of ethanol on the cerebellar adenylyl cyclase cascade from membrane to nucleus and to determine how this important signaling pathway neuroadapts during chronic ethanol expo-sure. An acute ethanol challenge increased cyclic AMP content and protein kinase A activity by 80 % compared to control rats. In the nucleus the phosphorylated form of cAMP responsive element binding protein (CREB) increased 500%. Gel retarda-tion assays with an oligomer encoding the rat proenkephalin cyclic AMP (CRE)1 were performed. Assays from protein de-rived from rats acutely exposed to ethanol identified three CRE-protein complexes also observed in assays of protein from saline-treated animals. However, after acute ethanol ex-posure, the intensity of the upper and middle CRE-protein complexes increased by 3-fold (280 ± 10 vs. 70 ± 3 arbitrar