Synergistic Effects of Adenosine A_2A Antagonist and L-DOPA on Rotational Behaviors in 6-Hydroxydopamine-Induced Hemi-Parkinsonian Mouse Model

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In this study, we examined the combination effects of L-DOPA and adenosine receptor antagonists on rotational behaviors in a hemi-Parkinsonian mouse model induced by unilateral 6-hydroxydopamine (6-OHDA) injection. The adenosine A_2A antagonist SCH-58261, but not the A₁-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine or A_2B-receptor antagonist alloxazine, synergistically potentiated the L-DOPA-induced rotational behaviors in the 6-OHDA-lesioned mice. In addtion, the 6-OHDA-induced lesions of the dopaminergic system did not affect the in vivo binding of an adenosine A_2A-receptor tracer [¹¹C]SCH-442416 in the striatatum. These findings suggest that adenosine A_2A antagonists are extremely useful for pharmacotherapy of L-DOPA in Parkinson’s disease patients.