Effects of A2A adenosine receptor blockade or stimulation on alcohol intake in alcohol-preferring rats

Psychopharmacology (Impact Factor: 4.06). 02/2012; 219(4):945-957. DOI: 10.1007/s00213-011-2430-1

ABSTRACT RationaleA2A adenosine receptors (A2AARs) have been proposed to be involved in drug addiction; however, preclinical studies about the effects of A2AAR ligands on alcohol consumption have provided inconsistent results.

ObjectivesThe present study evaluated the effect of intraperitoneal injections of the A2AAR antagonist ANR 94, and the A2AAR agonists CGS 21680 and VT 7 on voluntary drinking and operant self-administration of 10% ethanol in Marchigian Sardinian
alcohol-preferring (msP) rats.

ResultsVoluntary ethanol drinking was increased by ANR 94 in acute and subchronic experiments, while it was reduced by A2AAR agonists. The effect of CGS 21680 was abolished by a low dose of ANR 94, confirming its mediation by A2AARs. Ethanol self-administration was reduced by CGS 21680 and VT 7, while ANR 94 slightly but significantly increased it.
Blood alcohol levels were not modified by A2AAR agonists, indicating that their effect is not related to ethanol pharmacokinetics. The effect of VT 7 on ethanol drinking
was behaviourally selective; ethanol and food intake were reduced, but water intake was increased, and total fluid intake
was not different from that of controls. Moreover, VT 7 did not affect locomotor activity. CGS 21680 (0.1mg/kg) did not modify
total fluid intake, but 0.2 and 0.3mg/kg reduced total fluid intake and locomotor activity.

ConclusionThese results provide evidence that A2AAR agonists reduce ethanol consumption in msP rats, which represent an animal model of alcohol abuse related to stress, anxiety
and depression. A2AARs may represent a potential target for treatment of alcohol abuse.

KeywordsA2A Adenosine receptor–A2A Adenosine receptor agonist–A2A Adenosine receptor antagonist–Alcohol intake–Alcohol self-administration–Alcohol-preferring rats

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