Fetal mesencephalic grafts decrease the rate of dopamine uptake in the non-lesioned striatum of unilaterally 6-OHDA...

In the present study the influence of intraventricular fetal mesencephalic grafts on the elimination rate of extracellular dopamine (DA) in the non-lesioned striatum of previously unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats was investigated. The elimination of DA was measured after electrical stimulation of the medial forebrain bundle in vivo before and after treatment with the high affinity uptake inhibitor GBR 12909 (20 mg/kg i.p.) using fast cyclic voltammetry (FCV). Rotational behavior induced by amphetamine (AMPH, 2 mg/kg i.p.) and tyrosine hydroxylase (TH) immunohistochemistry were used to prove the functional recovery and the ingrowth of the graft, respectively. After grafting, the number of rotations was decreased and TH-positive cells and fibers were found in the grafted striatum. Voltammetric measurements with the aid of a kinetic model revealed a smaller rate constant for the in vivo elimination of extracellular DA in the non-lesioned striatum of grafted rats compared to that of non-grafted controls. This effect was abolished after treatment with GBR 12909. Our results will be discussed in relation to the method used and according to recent investigations of the specific [3H]DA uptake into striatal synaptosomes in vitro. Based on these data we conclude that grafts, placed to the lesioned striatum, reduce the DA uptake rate in the non-lesioned striatum due to the reduction of the number of functional DA transporters.