Rationale A2A 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. Objectives The 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. Results Voluntary 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, VT7 did not affect locomotor activity. CGS 21680 (0.1 mg/kg) did not modify total fluid intake, but 0.2 and 0.3 mg/kg reduced total fluid intake and locomotor activity. Conclusion These 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.

Effects of A(2A) adenosine receptor blockade or stimulation on alcohol intake in alcohol-preferring rats.

MICIONI DI BONAVENTURA, Maria Vittoria;CIFANI, Carlo;LAMBERTUCCI, Catia;VOLPINI, Rosaria;CRISTALLI, Gloria;
2012-01-01

Abstract

Rationale A2A 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. Objectives The 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. Results Voluntary 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, VT7 did not affect locomotor activity. CGS 21680 (0.1 mg/kg) did not modify total fluid intake, but 0.2 and 0.3 mg/kg reduced total fluid intake and locomotor activity. Conclusion These 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.
2012
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/232267
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