The novel adenosine A2a antagonist ST1535 potentiates the effects of a threshold dose Of L-dopa in unilaterally 6-OHDA-lesioned rats

Adenosine A2a antagonists can modulate dopamine-mediated motor behaviours, however, their ability to induce rotational behaviour in 6-hydroxydopamine (6-OHDA)-lesioned rats and to potentiate the effects of L-dopa differs. We now report on the effects of the novel A2a antagonist ST1535 on rotational responses in this model. When administered alone, ST1535 (2.5-40 mg/kg po) enhanced exploratory behaviour and produced a dose-related increase in ipsilateral rotation in rats with a unilateral 6-OHDA lesion of the nigro-striatal pathway. Administration of ST1535 (40 mg/kg po) in combination with a high dose Of L-dopa (12 mg/kg ip) caused marked contraversive rotation but did not alter the rotational response produced by L-dopa alone. In contrast, when administered in combination with L-dopa (7 mg/kg ip) that alone produced a submaximal circling response, ST1535 enhanced the intensity and duration of rotation. These results suggest that ST1535 is able to alter dopamine-mediated behaviour when given alone and to potentiate the effects of submaximal doses Of L-dopa. ST1535 may be useful in the treatment of Parkinson's disease and effective in reducing the use of L-dopa. (c) 2006 Elsevier B.V. All rights reserved.