ADENYLYL-CYCLASE SIGNAL-TRANSDUCTION AND ALCOHOL-INDUCED SEDATION

This study examined adenylyl cyclase (AC) signal transduction in alcoh ol-sensitive brain regions of rats selectively bred for high (HAD) and low (LAD) alcohol drinking and correlated these findings with differe nces in sensitivity and tolerance to alcohol-induced sedation found wi thin these lines. LAD rats were more sensitive to the sedative effects of alcohol than were HAD rats as evidenced by a shorter latency to lo se the righting response (RR) after a single alcohol challenge. When t ime to recover the RR was compared after each of two alcohol challenge s, HAD rats recovered the RR more rapidly following the second challen ge compared to the first, indicating that the HAD rats rapidly develop ed tolerance to the sedative effects of alcohol. Tolerance did not dev elop in rats of the LAD line. Two months after completion of behaviora l testing, adenylyl cyclase (AC) signal transduction was examined in a lcohol-sensitive brain regions of rats from both lines. Immunoblot ana lyses indicated that LAD rats had greater G(s) alpha expression in the frontal cortex (FC) and hippocampus (HIP) compared to HAD rats. Rats with the highest HIP and FC G(s) alpha levels were more rapidly affect ed by the sedative properties of alcohol than were rats with lower G(s ) alpha levels. G protein expression and AC activity in the FC, HIP, c erebellum (CERE), and nucleus accumbens (ACB) were also correlated wit h sensitivity to the sedative properties of alcohol and with the rapid development of tolerance to this alcohol effect. The results suggest that sensitivity and tolerance to alcohol-induced sedation may be medi ated in part through AC signal transduction. (C) 1997 Elsevier Science Inc.