Autoradiographic study of striatal D 1 and D 2 dopamine receptors in 6-OHDA-lesioned rats receiving foetal ventral mesencephalic grafts and chronic treatment with l-DOPA and carbidopa

Abstract

Foetal dopamine cell suspensions or sham preparations were implanted into the denervated striatum of rats with a unilateral 6-hydroxy-dopamine (6-OHDA) lesion of the medial forebrain bundle. Some animals were also treated with l-DOPA (200 mg/kg/24 h) and carbidopa (25 mg/kg/24 h) in the drinking water for 5 weeks, followed by a 3-week drug-free period. Rotational responses to apomorphine and (+)-amphetamine were assessed, and the density of D 1 and D 2 dopamine receptors was evaluated autoradiographically in striatal slices exposed to [ 3H]SCH 23390 or [ 3H]spiperone. Foetal grafts reduces apomorphine-induced contralateral rotation and prevented the development of apomorphine-induced stereotypy. Foetal grafts abolished (+)-amphetamine-induced ipsilateral rotation. These effects of the grafts were not altered by treatment with l-DOPA. A unilateral 6-OHDA lesion of the nigrostriatal pathway resulted in an ipsilateral increase in D 2 receptor density most marked in the lateral and dorsomedial quadrants of the striatum compared with the contralateral side. Foetal ventral mesencephalic grafts implanted into the lesioned striatum decreased D 2 receptor density to levels found in the contralateral intact striatum. Chronic l-DOPA and carbidopa treatment did not alter the effect of the grafts. A 6-OHDA lesion resulted in a reduction of D 1 receptor density in the lateral areas of the lesioned striatum at Level 2. The presence of a foetal ventral mesencephalic graft either alone or together with l-DOPA treatment did not alter the lesion-induced changes in D 1 binding density.