Modification of adenosine extracellular levels and adenosine A(2A) receptor mRNA by dopamine denervation

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.