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

Abstract

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)