Adenosine A1 and A2 receptors modulate extracellular dopamine levels in rat striatum

To clarify differences in the operating mechanisms of adenosine receptor subtypes (Al and A2), striatal extracellular dopamine levels under various conditions were determined by in vivo microdialysis. Adenosine (50 mu M) as well as the selective Al agonist, 2-chloro-N-6-cyclopentyladenosine (CCPA; 1 mu M ) decreased striatal extracellular dopamine levels, while the selective adenosine Al antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT; 50 mu M) and caffeine (100 mu M) increased striatal extracellular dopamine levels. A selective A2a agonist, 2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamideadenosine (CGS21680; 10 mu M), a selective A2 agonist, N-6-[2-(3,5-dimethoxyphenyl)-2-(methylphenyl)ethyl]adenosine (DPMA; 5 mu M) and a selective A2 antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX; 10 mu M), did not affect extracellular dopamine levels. When the Al receptor was blocked by CPT, extracellular dopamine levels were increased by adenosine and DPMA, decreased by caffeine as well as DMPX, and unaffected by CGS21680. These results indicate that the stimulatory effects of the A2 receptor on striatal extracellular dopamine levels are masked by the inhibitory effects of the Al receptor.