Abstract
Adenosine, acting on A(2A) adenosine receptors, regulates addictive processes induced by drugs of abuse. The present study investigates the role of A(2A) adenosine receptors in neurochemical and behavioural responses to an acute cocaine challenge. Changes in the extracellular levels of dopamine in the nucleus accumbens of mice lacking A(2A) adenosine receptors and wild type littermates after an acute cocaine (20mg/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 dopamine were not sustained in mice lacking A(2A) receptors in comparison to wild-type mice (P<0.05). Cocaine administration significantly increased ambulatory activity in both genotypes. However, overall locomotor activity was further increased whilst rest and small local movement measures were significantly attenuated in the A(2A) receptor knockout mice compared to wildtype littermates (P<0.05). Our findings support an important role for adenosine A(2A) receptor in modulating the acute effects of cocaine, as demonstrated by the decrease in cocaine-evoked dopaminergic transmission in the nucleus accumbens. Furthermore, the results support an important antagonistic role of A(2A) R in vivo in regulating psychostimulant-induced hyperlocomotion. Synapse, 2011. © 2011 Wiley-Liss, Inc.