Pre-treatment with dopamine agonists influence L-dopa mediated rotations without affecting abnormal involuntary movements in the 6-OHDA lesioned rat

L-dopa induced dyskinesia is a complication of long-term L-dopa administration in patients with Parkinson's disease. This study uses the rodent model of dyskinesia to determine whether prior dopamine agonist treatment causes long-term changes that influence the development of L-dopa mediated behaviours. Rats with unilateral 6-OHDA lesions were injected with dopamine agonists (ropinirole, piribedil bromocriptine, all 1 mg/kg) or saline (0.9%) daily for 21 days. Following a 1-week drug free interval L-dopa was administered for 15 days (10 mg/kg with benserazide 15 mg/kg in saline s.c.). Rotational behaviour and abnormal involuntary movements (AIMS) were recorded at regular intervals. All dopamine agonists induced a contralateral rotational response on day 1, which increased in response to repeated administration but did not by themselves induce overt dyskinesias. On day 1 of L-dopa administration animals pre-treated with piribedil and ropinirole produced a more severe rotational response. In the saline pre-treated group. AIMs developed with repeated L-dopa administration, which was reflected in the increased expression of PPE-B mRNA. There was a trend for the same pattern in the dopamine agonist treated groups but this was non-significant. Therefore, while locomotor sensitivity is altered by the pre-treatment with dopamine agonists, there appears to be no increased risk of developing AIMs. (C) 2010 Elsevier B.V. All rights reserved.