Blunt, Stavia Brigitte; (1992) The effect of chronic l-dopa treatment on the survival and function of foetal ventral mesencephalic grafts in rats with a unilateral 6-ohda lesion. Doctoral thesis (Ph.D.), University College London.

Text The_effect_of_chronic_l-dopa_t.pdf Download (12MB)

Abstract

The effect of chronic treatment with L-3,4- dihydroxyphenylalanine (L-DOPA) and a-methyl- dopahydrazine (carbidopa), at target doses of 200mg/kg/24h and 25mg/kg/24h respectively, on the survival and function of rat foetal ventral mesencephalic (VM) grafts in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway was assessed. Animals receiving foetal VM grafts showed a reduction of apomorphine-induced contralateral rotation, and abolition of (+)-amphetamine-induced ipsilateral rotation. This effect of the grafts was not altered by 5 weeks' treatment with L-DOPA and carbidopa. The foetal VM grafts prevented development of marked apomorphine- induced stereotypy which was otherwise seen in lesioned rats receiving sham grafts and L-DOPA treatment. Dopamine cell numbers and their morphology (assessed with tyrosine hydroxylase immunohistochemistry) and fibre outgrowth (assessed with 3H-mazindol autoradiography) were not affected by this treatment. Autoradiographic studies of specific 3H-spiperone and 3H-SCH 23390 binding to striatal slices demonstrated that a 6-OHDA lesion increased specific 3H-spiperone binding ipsilaterally, most marked in the lateral and dorsomedial quadrants of the mid-body of the striatum (Level 2). Specific 3H-SCH 23390 binding was inconsistently affected by the lesion apart from an ipsilateral decrease in the ventro-lateral quadrant of the mid-body of the striatum (Level 2). The lesion-induced changes in specific 3H-spiperone binding were reversed by foetal VM grafts, but not by L-DOPA and carbidopa treatment for 5 weeks. Specific 3H-SCH 23390 binding density was not affected by either foetal grafts or by L-DOPA treatment, or a combination of the two. L-DOPA and carbidopa treatment for 27 weeks of animals receiving foetal grafts did not interfere with the grafts' abilities to sustain abolition of (+)- amphetamine-induced ipsilateral rotation, and reduction of apomorphine-induced contralateral rotation. Dopamine cell survival in these grafts and their morphology were not affected by this treatment. However, within the grafts of animals treated with L-DOPA and carbidopa, the number of reactive astrocytes was increased. Also, L- DOPA treatment for 27 weeks resulted in a further reduction in the number of dopamine cells that remained in the ventral tegmental area ipsilateral to the 6-OHDA lesion.

Download activity - last month

Export as XMLCSVJSON

Download activity - last 12 months

Export as CSVXMLJSON

Downloads by country - last 12 months

Export as JSONCSVXML

Archive Staff Only

View Item