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In vivo dopaminergic and behavioral responses to acute cocaine are altered in adenosine A 2A receptor knockout mice

par Wells, Lisa;Opacka-Juffry, Jolanta;Fisher, Donald;Ledent, Catherine ;Hourani, Susanna;Kitchen, Ian
Référence Synapse, 66, 5, page (383-390)
Publication Publié, 2012-05

Article révisé par les pairs

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Résumé :

Adenosine, acting on adenosine A 2A receptors (A2ARs), regulates addictive processes induced by drugs of abuse. This study investigates the role of A 2A adenosine receptors in neurochemical and behavioral responses to an acute cocaine challenge. Changes in the extracellular levels of dopamine (DA) in the nucleus accumbens (NAc) of mice lacking A 2A adenosine receptors and wild type (WT) littermates after an acute cocaine (20 mg/kg) administration were evaluated by in vivo microdialysis studies. Locomotor effects induced by cocaine were measured during the microdialysis procedure. Cocaine-evoked increases in extracellular DA were not sustained in mice lacking A 2ARs in comparison with wild-type mice (P < 0.05). Cocaine administration significantly increased ambulatory activity in both genotypes. However, overall locomotor activity was further increased, whereas rest and small local movement measures were significantly attenuated in the A 2AR knockout mice compared with WT littermates (P < 0.05). Our findings support an important role for adenosine A 2AR in modulating the acute effects of cocaine, as demonstrated by the decrease in cocaine-evoked dopaminergic transmission in the NAc. Furthermore, the results support an important antagonistic role of A 2AR in vivo in regulating psychostimulant-induced hyperlocomotion. 2012. © 2011 Wiley Periodicals, Inc.