M. El Yacoubi et al., Absence of the adenosine A(2A) receptor or its chronic blockade decrease ethanol withdrawal-induced seizures in mice, NEUROPHARM, 40(3), 2001, pp. 424-432
Considering the existing interactions between ethanol and adenosine, the in
fluence of the genetic impairment of the adenosine A(2A) receptor has been
examined upon the seizures occurring at the cessation of chronic ethanol in
take or 'ethanol withdrawal' in male mice. Acute clearance of ethanol did n
ot differ between adenosine A(2A) receptor knockout and wild-type mice. Mic
e were exposed for 10 days to a diet consisting of a milky chocolate drink
that contained increasing concentrations (1.8, 3.6 and 6.3% V/V) Of ethanol
. Adenosine A(2A) receptor knockout mice ingested similar amounts of the fl
uid, either containing alcohol or not, as did the controls. The severity of
handling-induced convulsions during withdrawal was significantly reduced i
n the adenosine A(2A) receptor knockout mice as compared with their wild-ty
pe controls. The selective adenosine A(2A) receptor antagonist ZM 241385 (2
0 mg/kg) also significantly attenuated the intensity of withdrawal-induced
seizures occurring in wild-type male mice when intraperitoneally administer
ed twice daily during the last 5 days of the forced alcohol intake. These r
esults suggest that selective adenosine A(2A) receptor antagonists may be u
seful in the treatment of alcohol withdrawal. (C) 2001 Elsevier Science Ltd
. All rights reserved.