Adenosine agonists can both inhibit and enhance in vivo striatal dopamine release

The effects on striatal dopamine (DA) release and metabolism by local administration of adenosine analogues with different affinities for the A 1 and A 2 adenosine receptors, were investigated using the technique of microdialysis. 2-Chloroadenosine (2-CADO), decreased levels of both dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in striatal dialysates at concentrations of 1–10 μM; a similar effect was also seen after administration of N 6-(2-phenyl-isopropyl)adenosine (R(−)-PIA) and 5′-N-ethylcarboxamido-adenosine (NECA) at a concentration of 10 μM. The inhibitory action of 2-CADO on DA release and metabolism was blocked by the selective A 1 antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT), suggesting mediation by A 1 receptors. 2-CADO at a concentration of 100 μM increased levels of both DA and DOPAC in striatal perfusates, an effect which was not inhibited by CPT. This stimulatory action on extracellular DA concentration in striatum was also seen with 10 μM 5′-(N-cyclopropyl)-carboxamidoadenosine (CPCA) a relatively selective A 2 adenosine agonist. These results suggest that adenosine agonists enhance or depress striatal DA release depending on the nature and concentration of the drug.