The effect of chronic l-DOPA treatment on the recovery of motor function in 6-hydroxydopamine-lesioned rats receiving ventral mesencephalic grafts

Abstract

The effect of treatment for 5 weeks with l-DOPA (200 mg/kg/24h) plus carbidopa (25 mg/kg/24 h) on the behavioural recovery produced by rat fetal ventral mesencephalon grafts implanted into the striatum of 6-hydroxydopamine-lesioned rats was assessed. Animals with unilateral 6-hydroxy-dopamine lesions of the nigrostriatal pathway and a sham graft (Group A) showed persistent high rates of rotation in response to the administration of apomorphine (0.5 mg/kg s.c.) (contralateral rotation) or (+)-amphetamine (5 mg/kg i.p.) (ipsilateral rotation). Treatment of sham-grafted animals with l-DOPA plus carbidopa had no effect on the rate of rotation to apomorphine or (+)-amphetamine (Group B). The proportion of animals showing marked stereotypy following apomorphine administration was greater in sham-grafted animals receiving l-DOPA and carbidopa than in sham-grafted animals alone. Animals receiving unilateral 6-hydroxydopamine lesions followed by a fetal graft (Group C) showed a reduction in apomorphine-induced contralateral rotation and a complete reversal of (+)-amphetamine-induced ipsilateral rotation when assessed 6 weeks later. The reductions in apomorphine- and (+)-amphetamine induced rotational behaviour produced by the fetal graft in animals with a 6-hydroxydopamine lesion were not altered by treatment with l-DOPA plus carbidopa (Group D). The proportion of animals showing marked apomorphine-induced stereotypy did not change significantly in either group over time. In rats with a unilateral 6-hydroxydopamine lesion receiving fetal dopamine grafts, treatment with high doses of l-DOPA and carbidopa for 5 weeks does not have a detrimental effect on the functional activity of the grafts as assessed by reduction of apomorphine- and (+)-amphetamine-induced motor asymmetry. The continuation of l-DOPA therapy may not adversely affect fetal graft survival and growth in patients with Parkinson's disease.