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

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 2A Rs 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 2A R knockout mice compared with WT littermates ( P < 0.05). Our findings support an important role for adenosine A 2A R 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 2A R in vivo in regulating psychostimulant‐induced hyperlocomotion. Synapse, 2012. © 2011 Wiley Periodicals, Inc.