Alterations in brain cyclic guanosine 3':5'-monophosphate levels after acute and chronic treatment with ethanol.

A previous finding from our laboratory, that a single dose of ethanol depletes cerebellar cyclic guanosine 3':5'-monophosphate (cGMP), has now been extended to an investigation of the effects of acute and chronic ethanol treatment of cGMP levels in six areas of the rat brain. Rats were either gavaged with a single dose of ethanol (6g/kg) or rendered ethanol-dependent with 11 to 15 g/kg/day in 3 to 5 fractions over a 4-day period. A single dose of ethanol depleted cGMP levels in only five areas of the brain studied. In the two areas in which a time course of the response was determined, the caudate nucleus and cerebral cortex, cGMP depletion was maximal 1 hour after ethanol administration when blood ethanol concentrations were highest. cGMP levels returned to control values as blood ethanol was eliminated. Inethanol-dependent animals still intoxicated, cGMP was reduced but not to the same magnitude in the cerebellum and brain stem when compared with the response obtained after a single dose at equivalent blood ethanol concentrations. During the ethanol withdrawal syndrome cGMP levels had returned to control vlaues. The data suggest that cBMP depletion may play a role in ethanol-induced intoxication and that tolerance to this effect develops concurrently with behavioral tolerance.