Adenosine A2A receptor antagonism potentiates L-DOPA-induced turning behaviour and c-fos expression in 6-hydroxydopamine-lesioned rats.

In order to investigate the role of adenosine A2A receptor blockade on dopamine-mediated motor responses, contralateral turning behaviour and expression of the early-gene c-fos was evaluated in rats with a unilateral 6-hydroxydopamine lesion of the dopaminergic nigrostriatal pathway. SCH 58261, (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1 , 5-c]pyrimidine) a potent and selective antagonist of adenosine A2A receptors (5 mg/kg i.p.), induced a 70-fold increase in the contralateral turning behaviour induced by a low dose (2 mg/kg i.p.) of the dopamine precursor L-DOPA (L-3, 4-dihydroxyphenylalanine). Expression of c-fos as measured by Fos-like immunoreactivity after SCH 58261 plus L-DOPA was also potentiated as compared with L-DOPA alone, both in striatum and globus pallidus of the 6-hydroxydopamine-lesioned side of the brain. SCH 58261 induced a less marked potentiation (7-fold) of turning behaviour induced by dopamine D2 receptor stimulation with quinpirole, while Fos-like immunoreactivity in the striatum and globus pallidus was not affected. Previous studies have shown that SCH 58261 strongly potentiated dopamine D1 receptor-mediated responses. The results of the present study therefore indicate that the positive interaction between SCH 58261 and L-DOPA, in 6-hydroxydopamine-lesioned rats, is mainly due to an interaction with dopamine D1 receptors. The data also suggest that adenosine A2A receptor antagonists might be useful for potentiating the effects of L-DOPA in Parkinson's disease.