Role of adenosine A1 and A2A receptors in the alcohol withdrawal syndrome

The role of adenosine receptor-mediated signaling was examined in the alcohol withdrawal syndrome. CD-1 mice received a liquid diet containing ethanol (6.7%, v/v) or a control liquid diet that were abruptly discontinued after 14 days of treatment. Mice consuming ethanol showed a progressive increase in signs of intoxication throughout the drinking period. Following abrupt discontinuation of ethanol diet, mice demonstrated reversible signs of handling-induced hyperexcitability that were maximal between 5-8 h. Withdrawing mice received treatment with adenosine receptor agonists at the onset of peak withdrawal (5.5 h) and withdrawal signs were blindly rated (during withdrawal hours 6 and 7). Adenosine A(1)-receptor agonist R-N-6(phenylisopropyl)adenosine (0.15 and 0.3 mg/kg) reduced withdrawal signs 0.5 and 1.5 h after drug administration in a dose-dependent fashion. Adenosine A(2A)-selective agonist 2-p-(2-carboxethyl)phenylethyl-amino-5' -N-ethylcarboxamidoadenosine (0.3 mg/kg) reduced withdrawal signs at both time points. In ethanol-withdrawing mice, there were significant decreases in adenosine transporter sites in striatum without changes in cortex or cerebellum. In ethanol-withdrawing mice, there were no changes in adenosine A(1) and A(2A) receptor concentrations in cortex, striatum, or cerebellum. There appears to be a role for adenosine A(1) and A(2A) receptors in the treatment of the ethanol withdrawal syndrome. Published by Elsevier Science Inc.