Autoradiographic study of striatal D1 and D2 dopamine receptors in 6-OHDA-lesioned rats receiving foetal ventral mesencephalic grafts and chronic treatment with L-dopa and carbidopa.
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 D1 and D2 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 D2 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 D2 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 D1 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 D1 binding density.
Blunt
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Parkinson's Disease Society Experimental Research Laboratories, King's College, London, UK.
Jenner
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P
Marsden
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CD
D000818:Animals; D001058:Apomorphine; D001345:Autoradiography; D016380:Brain Tissue Transplantation / Q000502:physiology*; D002230:Carbidopa / Q000008:administration & dosage; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects; D003913:Dextroamphetamine; D005260:Female; D016332:Fetal Tissue Transplantation / Q000502:physiology*; D066298:In Vitro Techniques; D007980:Levodopa / Q000008:administration & dosage; D008636:Mesencephalon / Q000637:transplantation*; D016627:Oxidopamine; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000032:analysis / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000187:drug effects*; D013997:Time Factors
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D007980:Levodopa; D016627:Oxidopamine; D002230:Carbidopa; D001058:Apomorphine; D003913:Dextroamphetamine