Effect of acute L-dopa pretreatment on apomorphine-induced rotational behavior in a rat model of Parkinson's disease

Currently, reduction of apomorphine-induced rotational behavior in the B-hy droxydopamine (6-OHDA) lesioned rat is the most utilized drug-induced parad igm for assessing functional efficacy in a rat model of Parkinson's disease (PD). Any clinically predictive animal model of PD should include a positi ve response to L-dopa, the standard pharmacotherapy for PD. However, the ac ute interaction between L-dopa and apomorphine has never been studied to de termine if L-dopa pretreatment could reduce apomorphine-induced rotational behavior in a 6-OHDA lesioned rat. The present study was designed to explor e whether, indeed, pretreatment with subrotational doses of L-dopa could in hibit apomorphine-induced rotations. The data indicate that L-dopa signific antly reduced apomorphine-induced rotational behavior only at one dose (5.0 mg/kg) for 12 min. Based on these and other data, it is concluded that alt hough the apomorphine-induced rotational paradigm may continue to be utiliz ed as one additional indicator of efficacy in the 6-OHDA rat model of PD, i t is not in itself a completely valid functional assay. (C) 2000 Academic P ress.