G-PROTEIN PATTERN AND ADENYLYL-CYCLASE ACTIVITY IN THE BRAIN OF RATS AFTER LONG-TERM ETHANOL

Previous studies have described changes in levels of GTP binding prote ins (G-proteins) following exposure of rodents to ethanol that did not correlate with the altered activation of the transmembrane signaling pathway. Possible reasons for these inconsistencies were taken into ac count in the present study by measuring the levels of four different G -protein subunits (G(alpha s), G(alpha i1/2), G(alpha o), G(beta gamma )) in six brain regions. Rats were exposed to ethanol for 4 weeks (for ced intake of ethanol liquid diet) and 40 weeks (free-choice ethanol). G-protein levels and activation of adenylyl cyclase (AC) were measure d on day 1, day 8, and day 28 after withdrawal. When there were change s in the G-protein levels at all, increases were observed mostly in br ain regions from rats with the 40-week exposure and decreases in regio ns from rats with the 4-week exposure that consumed a higher amount of ethanol per day. In some regions the changes had not normalized by da y 28 in the 40-week ethanol group whereas in the 4-week ethanol group changes were observed only at day 1 and day 8. Activation of AC was di sturbed in the 4-week ethanol group. Reduced activation was detected i n membranes of the cerebral cortex, whereas increased activation was o bserved in the cerebellum, hypothalamus, pens, and striatum. Addition of ethanol (100 mM) to the tissue homogenate facilitated the stimulati ng action of Gpp(NH)p only in the hippocampus, cerebellum, and striatu m. This in vitro action of ethanol was not affected by the longterm et hanol exposure. Activation of AC in the 40-week ethanol group was redu ced in the cerebral cortex, pens, and striatum and increased in the ce rebellum and hypothalamus if changes occurred at all. The findings sup port the contention that changes of the transmembrane signaling pathwa y in ethanol-exposed rats depend on the brain region and on the mode o f application. Furthermore, a clear dissociation was observed between changes of the activation of the adenylyl cyclase and the changes in t he levels of G-proteins. (C) 1998 Elsevier Science Inc.