EFFECTS OF ACUTE ETHANOL ADMINISTRATION ON POLYPHOSPHOINOSITIDE TURNOVER AND LEVELS OF INOSITOL 1,4,5-TRISPHOSPHATE IN MOUSE CEREBRUM AND CEREBELLUM

Although ethanol is known for its central depressant action, its effec t on the polyphosphoinositide (poly-PI) signal transduction activity i n brain has not been examined in detail. In this study, C57BI/6J mice were injected intracerebrally with [H-3]inositol, and poly-PI turnover in brain was assessed by determining the levels of labeled inositol m onophosphates (IP1) accumulated after intraperitoneal injection of LiC l (6 meq/kg body weight) 4 hr before killing. Using this experimental protocol, acute ethanol administration (by gavage) resulted in time- a nd dose-dependent decreases in the levels of labeled IP1 in both cereb rum and cerebellum as compared with controls. The ethanol-induced decr ease in labeled IP1 correlated well with the decrease in levels of ino sitol 1,4,5-triphosphate (as measured by the radioreceptor assay) and the increase in blood ethanol concentration. Despite a 4-fold higher a ccumulation of labeled IP1 in the cerebrum compared with the cerebellu m, there were no major differences in the steady-state levels of inosi tol 1,4,5-triphosphate (based on tissue weight) in either brain region . Intraperitoneal injection of atropine (50 mg/kg) (a muscarinic choli nergic receptor antagonist) to the lithium-treated mice resulted in a 34% decrease in labeled IP, as compared with controls. This result sug gests that a substantial proportion of the signals transduced were due to activation of the muscarinic cholinergic receptor. Administration of ethanol (5 g/kg) to the atropine-treated mice resulted in a further decrease in labeled IP, and longer sleep time as compared with those given ethanol alone. Taken together, these results indicate a relation ship between the acute effect of ethanol and the poly-PI signaling act ivity in brain and modulation of the ethanol effect by compounds affec ting the poly-PI signaling pathway.