Absence of the adenosine A(2A) receptor or its chronic blockade decrease ethanol withdrawal-induced seizures in mice

Citation
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
Citations number
46
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROPHARMACOLOGY
ISSN journal
00283908 → ACNP
Volume
40
Issue
3
Year of publication
2001
Pages
424 - 432
Database
ISI
SICI code
0028-3908(200103)40:3<424:AOTAAR>2.0.ZU;2-Y
Abstract
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.