The effect of L-dopa and carbidopa treatment on the survival of rat fetal dopamine grafts assessed by tyrosine hydroxylase immunohistochemistry and [3H]mazindol autoradiography.
The effect of treatment with L-3,4-dihydroxyphenylalanine (L-DOPA) and carbidopa for five weeks on the survival of rat fetal dopaminergic ventral mesencephalon cells implanted into the denervated striatum of rats with unilateral 6-hydroxydopamine nigrostriatal lesions was assessed. Rats receiving unilateral nigral 6-hydroxydopamine lesions followed by sham striatal grafts (Groups A and B) showed no recovery of (+)-amphetamine- or apomorphine-induced motor asymmetry. Rats in Group B (receiving treatment with L-DOPA and carbidopa) showed an increase in apomorphine-induced contralateral rotation and stereotypy. Animals receiving unilateral nigral 6-hydroxydopamine lesions followed by fetal striatal dopamine grafts (Groups C and D) showed complete recovery of (+)-amphetamine-induced rotation and a decrease of apomorphine-induced contralateral rotation. Treatment of animals in Groups B and D with L-DOPA (200 mg/kg per 24 h) and carbidopa (25 mg/kg per 24 h) by mouth for five weeks had no effect on the behavioural response to (+)-amphetamine. In the 6-hydroxydopamine-lesioned animals there was loss of tyrosine hydroxylase-immunoreactive cells in substantia nigra and ventral tegmental area of greater than 97% and to 66%, respectively, compared to the intact side. The number and morphology of tyrosine hydroxylase-immunoreactive cells in the intact substantia nigra and ventral tegmental area was not altered by treatment with L-DOPA and carbidopa. In the 6-hydroxydopamine-lesioned striatum of rats receiving a sham graft (Group A) or a sham graft and treatment with L-DOPA and carbidopa (Group B) there were no tyrosine hydroxylase-positive cells or fibres visible.(ABSTRACT TRUNCATED AT 250 WORDS)
Parkinson's Disease Society Experimental Research Laboratories, King's College, London, U.K.
S B
SB
Blunt
P
P
Jenner
C D
CD
Marsden
D000818:Animals; D001345:Autoradiography; D016380:Brain Tissue Transplantation / Q000502:physiology*; D002230:Carbidopa / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D016332:Fetal Tissue Transplantation / Q000502:physiology*; D006085:Graft Survival / Q000187:drug effects*; D007150:Immunohistochemistry; D007980:Levodopa / Q000494:pharmacology*; D008454:Mazindol; D051381:Rats; D011919:Rats, Inbred Strains; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D007980:Levodopa; D008454:Mazindol; D014446:Tyrosine 3-Monooxygenase; D002230:Carbidopa; D004298:Dopamine