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.