Agonists of A1 and A2A adenosine receptors attenuate methamphetamine-induced overflow of dopamine in rat striatum.

The effect of adenosine receptor agonists on the release of striatal dopamine (DA), induced by repeated doses of methamphetamine (MTH), was evaluated. Rats received three injections of MTH (5 mg/kg i.p.) at 2-h intervals. The release of DA in the striatum was measured by a microdialysis in freely moving animals. The agonist of adenosine A1 receptor, N6-cyclopentyladenosine (CPA) and the agonist of adenosine A2A receptor, 2-[p-(carboxy-ethyl)phenylethylamino]-5'-N-ethylcarboxyamidoade nosine (CGS 21680), either of them being infused locally into the striatum at concentrations of 50 and 100 microM, produced decreases in the extracellular DA level during exposure to MTH, and a weaker effect on the levels of DOPAC and HVA. The above effects were reversed by the specific antagonists of adenosine A1 and A2A receptors, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and 3, 7-dimethyl-1-propargylxanthine (DMPX), respectively. Our results indicate that both the A1 and A2A adenosine receptors appear to be involved in reducing the excessive release of DA in the striatum; furthermore, they suggest a neuroprotective role of adenosine in MTH neurotoxicity.