Adenosine A1 receptor blockade mimics caffeine's attenuation of ethanol-induced motor incoordination.
The effects of co-administration of caffeine and ethanol were assessed on the motor coordination of rats on the accelerating rotarod (accelerod). Ethanol (2.5 g/kg, orally) decreased motor performance on the accelerod. Co-administration of caffeine (5 and 20 mg/kg, orally) dose-dependently attenuated this ethanol-induced deficit. Caffeine (20 mg/kg, orally) alone did not affect motor performance in the test. As caffeine is a non-selective adenosine receptor antagonist the ability of adenosine A(1) and A(2A) receptor blockade to attenuate ethanol-induced motor incoordination was determined. Pre-treatment with the adenosine A(1) receptor antagonist DPCPX (5 mg/kg, intraperitoneally) attenuated ethanol (2.5 g/kg, orally)-induced motor incoordination. By contrast, prior administration of the adenosine A(2A) selective antagonist SCH 58261 (10 mg/kg intraperitoneally) had no effect on the ethanol-induced motor deficit. These data demonstrate that adenosine A(1) receptor blockade mimics the inhibitory action of caffeine on ethanol-induced motor incorordination, and may contribute to the ability of caffeine to offset the acute intoxicating actions of ethanol.
Connole
Laura
L
Department of Safety Pharmacology, H. Lundbeck A/S, Valby, Copenhagen, Denmark.
Harkin
Andrew
A
Maginn
Mark
M
D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004347:Drug Interactions; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D009048:Motor Skills / Q000187:drug effects; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058916:Adenosine A1 Receptor Antagonists; D002492:Central Nervous System Depressants; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D014230:Triazoles; D014970:Xanthines; D002110:Caffeine; D000431:Ethanol; C051360:1,3-dipropyl-8-cyclopentylxanthine