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

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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, VT 7 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.

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Acknowledgments

The authors wish to thank Marino Cucculelli, University of Camerino, for msP breeding and Marcello Cippitelli, University of Macerata, for BAL measurements.

Conflicts of interest

The authors state no conflicts of interest.

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Authors and Affiliations

  1. School of Pharmacy, Pharmacology Unit, University of Camerino, 62032, Camerino, Macerata, Italy

    Maria Vittoria Micioni Di Bonaventura, Carlo Cifani & Maurizio Massi

  2. School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, 62032, Camerino, Macerata, Italy

    Catia Lambertucci, Rosaria Volpini & Gloria Cristalli

  3. Institute of Legal Medicine, University of Macerata, 62100, Macerata, Italy

    Rino Froldi

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  1. Maria Vittoria Micioni Di Bonaventura
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  2. Carlo Cifani
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Correspondence to Maria Vittoria Micioni Di Bonaventura.

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Micioni Di Bonaventura, M.V., Cifani, C., Lambertucci, C. et al. Effects of A2A adenosine receptor blockade or stimulation on alcohol intake in alcohol-preferring rats. Psychopharmacology 219, 945–957 (2012). https://doi.org/10.1007/s00213-011-2430-1

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