The effect of chronic L-dopa treatment on the recovery of motor function in 6-hydroxydopamine-lesioned rats receiving ventral mesencephalic grafts.
The effect of treatment for 5 weeks with L-DOPA (200 mg/kg/24 h) plus carbidopa (25 mg/kg/24 h) on the behavioral recovery produced by rat fetal ventral mesencephalon grafts implanted into the striatum of 6-hydroxydopamine-lesioned rats was assessed. Animals with unilateral 6-hydroxydopamine 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.
Blunt
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Parkinson's Disease Society Experimental Research Laboratories, King's College, Manresa Road, London, U.K.
Jenner
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P
Marsden
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CD
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002230:Carbidopa / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004326:Drinking / Q000187:drug effects; D005260:Female; D016332:Fetal Tissue Transplantation; D006892:Hydroxydopamines / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology*; D008636:Mesencephalon / Q000196:embryology*; D009043:Motor Activity / Q000187:drug effects*; D009420:Nervous System / Q000187:drug effects; D016627:Oxidopamine; D010300:Parkinson Disease; D051381:Rats; D012399:Rotation; D013239:Stereotyped Behavior / Q000187:drug effects; D013997:Time Factors
D006892:Hydroxydopamines; D007980:Levodopa; D016627:Oxidopamine; D002230:Carbidopa; D001058:Apomorphine