Possible role of adenosine in the CNS effects of ethanol

The ability of adenosine to modify the CNS effects of acute and chronic ethanol was studied by using theophylline, an adenosine antagonist, and dipyridamole, a blocker of adenosine reuptake. We also studied the binding characteristics of adenosine using crude membranes of whole brain. Theophylline pretreatment prior to acute ethanol administration markedly reduced the duration of ethanol-induced sleep and similarly decreased the intensity and duration of motor incoordination. In chronic ethanol treated mice the effect of theophylline on ethanol-induced hypnosis and motor incoordination was similar to the acute experiment. Dipyridamole markedly prolonged the duration of ethanol-induced hypnosis and potentiated the motor incoordination produced by acute ethanol. However, in chronic ethanol treated mice dipyridamole was not able to potentiate the motor incoordinating effect of ethanol although it was able to prolong ethanol hypnosis similar to the results obtained in the acute ethanol study. Neither drug had any effect on ethanol-induced hypothermia, in either the acute or chronic studies. After 10 days of ethanol ingestion the adenosine dissociation constant was unchanged whereas the number of brain adenosine receptors was increased 28% although the increase did not reach statistical significance. The number of adenosine receptors was reduced 40% at 24 and 48 h after withdrawal and returned to prewithdrawal levels at 72 h. The dissociation constant was reduced at 24 and 48 h but by 72 h had returned to prewithdrawal levels. The marked changes in adenosine binding characteristics as well as the modification of some CNS effects of ethanol by drugs which influence either adenosine binding to its receptor or the availability of adenosine suggests that adenosine may be involved in the expression of some of the CNS effects of ethanol.