Abstract
Adenosine A 2A receptor antagonists have been proposed as an effective therapy in the treatment of Parkinson's disease. To explore the possibility that dopamine denervation may produce modifications in adenosine A 2A transmission, we measured the extracellular concentration of adenosine and adenosine A 2A receptor mRNA in the striatum of rats infused unilaterally with 6-hydroxydopamine in the medial forebrain bundle. Fifteen days after 6-hydroxydopamine infusion, extracellular adenosine levels, measured by in vivo microdialysis, were significantly lower (−35%) in the dopamine-denervated striatum. At the time of the decrease in adenosine levels, an increase in striatal adenosine A 2A receptor mRNA levels (+20%), measured by in situ hybridization, was observed. Modifications in adenosine A 2A transmission, following nigrostriatal dopamine neuron degeneration, establish a potential neural basis for the effectiveness of adenosine A 2A receptor antagonists in the treatment of Parkinson's disease.
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