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 A1 and A2 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 microM; a similar effect was also seen after administration of N6-(2-phenylisopropyl)adenosine (R(-)-PIA) and 5'-N-ethylcarboxamido-adenosine (NECA) at a concentration of 10 microM. The inhibitory action of 2-CADO on DA release and metabolism was blocked by the selective A1 antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT), suggesting mediation by A1 receptors. 2-CADO at a concentration of 100 microM 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 microM 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA) a relatively selective A2 adenosine agonist. These results suggest that adenosine agonists enhance or depress striatal DA release depending on the nature and concentration of the drug.