5-HT2C receptor antagonists enhance the behavioural response to dopamine D-1 receptor agonists in the 6-hydroxydopamine-lesioned rat

Non-dopaminergic therapies are of potential interest in the treatment of Pa rkinson's disease given the complications associated with current dopamine- replacement therapies. In this study we demonstrate that SE 206553 (5-methy l-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrol[2,3-f]indole) (20 mg/kg) enhanced the actions of the dopamine D-1 receptor agonist, SKF 82958 ((+)-6 -chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine hydrobromide) (1 mg/kg), in eliciting locomotion in the 6-hydroxydopamine- lesioned rat model of Parkinson's disease. This action was only seen follow ing prior priming with L-DOPA (L-3,4-dihydroxyphenylalanine). SB 206553 had no effect on rotational behaviour when given alone. 5-HT2C receptor antago nists may have potential as a means of reducing reliance on dopamine replac ement in the treatment of Parkinson's disease. (C) 2000 Published by Elsevi er Science B.V. All rights reserved.