Involvement of A2Areceptors in anxiolytic, locomotor and motivational properties of ethanol in mice
Genes, Brain and Behavior. 2008-11-01; 7(8): 887-898
DOI: 10.1111/j.1601-183x.2008.00427.x
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1. Genes Brain Behav. 2008 Nov;7(8):887-98.
Involvement of A2A receptors in anxiolytic, locomotor and motivational properties
of ethanol in mice.
Houchi H(1), Warnault V, Barbier E, Dubois C, Pierrefiche O, Ledent C, Daoust M,
Naassila M.
Author information:
(1)Equipe Région INSERM 24, Groupe de Recherche sur l’Alcool et les
Pharmacodépendances, Université de Picardie Jules Verne, Faculté de Pharmacie,
Amiens, France.
We have shown previously that mice lacking the adenosine A2A receptor (A2AR)
generated on a CD1 background self-administer more ethanol and exhibit
hyposensitivity to acute ethanol. We aimed to investigate if the increased
propensity of A2A(-/-) mice to consume ethanol is associated with an altered
sensitivity in the motivational properties of ethanol in the conditioned place
preference (CPP) and conditioned taste aversion (CTA) paradigms and with an
altered development of sensitization to the locomotor effects of ethanol. We also
tested their sensitivity to the anxiolytic effects of ethanol. Our results show
that A2A(-/-) mice produced on a CD1 background displayed a reduced
ethanol-induced CPP and an increased sensitivity to the anxiolytic and
locomotorstimulant effects of ethanol, but they did not show alteration in
ethanol-induced CTA and locomotor sensitization. Ethanol-induced CPP, ethanol
consumption and the locomotor effects of ethanol were also tested in A2A(-/-)
mice produced on a C57BL/6J background. Our results emphasized the importance of
the genetic background because alteration in ethanol consumption and preference,
ethanol-induced CPP and locomotor-stimulant effects were not found in knockout
mice produced on the alcohol-preferring C57BL/6J genetic background. Finally, the
A2AR agonist,
2-p-(2-carboxyethyl)-phenylethylamino-50-N-ethylcarboxamidoadenosine
hydrochloride (CGS 21680), reduced ethanol consumption and preference in C57BL/6J
mice. In conclusion, A2AR deficiency in mice generated on a CD1 background leads
to high ethanol consumption that is associated with an increased sensitivity to
the locomotor-stimulant/anxiolytic effects of ethanol and a decrease in
ethanol-induced CPP.
DOI: 10.1111/j.1601-183x.2008.00427.x
PMID: 19097273 [Indexed for MEDLINE]