J Vaugeois | PubMed Health

PubMed2001

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

Considering the existing interactions between ethanol and adenosine, the influence of the genetic impairment of the adenosine A(2A) receptor has been examined upon the seizures occurring at the cessation of chronic ethanol intake or 'ethanol withdrawal' in male mice. Acute clearance of ethanol did not differ between adenosine A(2A) receptor knockout and wild-type mice. Mice 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 fluid, either containing alcohol or not, as did the controls. The severity of handling-induced convulsions during withdrawal was significantly reduced in the adenosine A(2A) receptor knockout mice as compared with their wild-type controls. The selective adenosine A(2A) receptor antagonist ZM 241385 (20 mg/kg) also significantly attenuated the intensity of withdrawal-induced seizures occurring in wild-type male mice when intraperitoneally administered twice daily during the last 5 days of the forced alcohol intake. These results suggest that selective adenosine A(2A) receptor antagonists may be useful in the treatment of alcohol withdrawal.

Administration, Oral↗

PubMed2000

SCH 58261 and ZM 241385 differentially prevent the motor effects of CGS 21680 in mice: evidence for a functional 'atypical' adenosine A(2A) receptor.

The acute motor effects elicited by drugs acting upon adenosine A(2A) receptors, namely the highly selective agonist CGS 21680 or the antagonists SCH 58261 and ZM 241385, were investigated in mice. CGS 21680 dose-dependently (0.1-2.5 mg/kg i.p.) decreased horizontal and vertical motor activities. The depressant effect of CGS 21680 (0. 5 mg/kg i.p.) was maintained in mice pretreated by the adenosine receptor antagonist 8-(p-sulfophenyl)-theophylline (10-30 mg/kg i.p. ), which poorly penetrates the blood-brain barrier, but was completely lost in adenosine A(2A) receptor knockout mice. Thus, the adenosine A(2A) receptor is critically involved in motor activity. SCH 58261 (1-10 mg/kg i.p.) increased locomotion and rearing with a quick onset, but for a shorter period in mice habituated to the environment than in mice unfamiliar to it. ZM 241385 (7.5-60 mg/kg i. p.) stimulated horizontal and vertical activities with a slow onset at the two highest tested doses, similarly in naive and in habituated mice. The increase in locomotion elicited by ZM 241385 (15-30 mg/kg i.p. and 10-20 nM i.c.v.) was retained in mice treated by CGS 21680 (0.5 mg/kg i.p.) but that elicited by SCH 58261 (1-3-10 mg/kg i.p. and 10-20 nM i.c.v.) partially subsided. In conclusion, both 'striatal-like'/'SCH 58261-sensitive' adenosine A(2A) receptors and 'ZM 241385-sensitive'/'atypical' CGS 21680 binding sites may mediate CGS 21680-induced motor effects. Moreover, our results suggest that 'atypical' CGS 21680 binding sites could be adenosine A(2A) receptors with a peculiar pharmacological profile.

Adenosine↗