title: Effects of A₂A adenosine receptor blockade or stimulation on alcohol intake in alcohol-preferring rats.
abstract: BACKGROUND
  A(2A) adenosine receptors (A(2A)ARs) have been proposed to be involved in drug addiction; however, preclinical studies about the effects of A(2A)AR ligands on alcohol consumption have provided inconsistent results.
  
  
  OBJECTIVE
  The present study evaluated the effect of intraperitoneal injections of the A(2A)AR antagonist ANR 94, and the A(2A)AR 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 A(2A)AR agonists. The effect of CGS 21680 was abolished by a low dose of ANR 94, confirming its mediation by A(2A)ARs. 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 A(2A)AR 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.
  
  
  CONCLUSIONS
  These results provide evidence that A(2A)AR agonists reduce ethanol consumption in msP rats, which represent an animal model of alcohol abuse related to stress, anxiety and depression. A(2A)ARs may represent a potential target for treatment of alcohol abuse.
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, 62032 Camerino, Macerata, Italy. mariavittoria.micioni@unicam.it
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Micioni Di Bonaventura
authors.forename: Carlo
authors.initials: C
authors.lastname: Cifani
authors.forename: Catia
authors.initials: C
authors.lastname: Lambertucci
authors.forename: Rosaria
authors.initials: R
authors.lastname: Volpini
authors.forename: Gloria
authors.initials: G
authors.lastname: Cristalli
authors.forename: Rino
authors.initials: R
authors.lastname: Froldi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Massi
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000428:Alcohol Drinking; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D016503:Drug Delivery Systems; D004435:Eating / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000187:drug effects / Q000378:metabolism*; D012646:Self Administration; D013872:Thionucleosides / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: C572126:5'-N-ethylcarboxamido-2-(2-phenethylthio)adenosine; C502530:8-ethoxy- 9-ethyladenine; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D013872:Thionucleosides; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000431:Ethanol; D000225:Adenine; D000241:Adenosine