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D Schönfuss

Publications and source records attributed to D Schönfuss.

4 recordsLinked to original sources

Modelling constant potential amperometry for investigations of dopaminergic neurotransmission kinetics in vivo.

Constant potential amperometry (CPA) was used for in vivo recording of extracellular dopamine (DA) after electrical stimulation of the medial forebrain bundle (MFB) (4 pulses, 2 mA, 20 or 100 Hz) in the striatum of the rat brain. CPA signals were analysed in the absence and presence of the DA uptake inhibitor nomifensine with the help of a mathematical model which considered both the influence of DA diffusion after its stimulated release and the Michaelis-Menten kinetics of cellular DA uptake from the extracellular space. We found an excellent conformity of experimentally obtained CPA signals and calculated curves. Mathematical analysis revealed that CPA signals were strongly influenced by DA diffusion. The kinetic parameters calculated from CPA signals in this study were in agreement with experimental determinations of Vmax and Km of extracellular DA uptake in other studies and reflect the particular pharmacological properties of nomifensine. CPA is a useful and efficient method for in vivo estimation of individual changes of DA kinetic parameters by pharmacological treatment.

Animals↗

Foetal ventral mesencephalic cell suspension grafts to the 6-hydroxydopamine-lesioned rat reduce the rate of dopamine uptake in the contralateral striatum.

The present study employed fast cyclic voltammetry, at carbon-fibre microelectrodes, to monitor and compare the rate of dopamine uptake in the rat striatum contralateral to (a) the 6-hydroxydopamine (6-OHDA)-lesioned/grafted striatum and (b) the 6-OHDA-lesioned/ sham grafted striatum. Cell suspensions of foetal rat ventral mesencephalic tissue were grafted into the dopamine-depleted striatum of unilaterally 6-OHDA-lesioned rats. Six weeks after grafting, animals with functional, mature grafts were monitored for dopamine elimination in the contralateral striatum following electrical stimulation of the median forebrain bundle, before and after treatment with the dopamine uptake inhibitor GBR 12909. Compared to animals with sham grafts, amphetamine-amplified rotational behaviour was significantly reduced in animals with grafts of foetal ventral mesencephalic tissue. Fast cyclic voltammetric measurements followed by evaluation with the aid of a kinetic model revealed that in grafted animals, the rate of dopamine uptake via the high affinity uptake mechanism, following treatment with GBR 12909, was significantly reduced when compared to sham grafted animals.

Amphetamine↗

Fetal mesencephalic grafts decrease the rate of dopamine uptake in the non-lesioned striatum of unilaterally 6-OHDA lesioned rats: an in vivo voltammetric study.

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.

Analysis of Variance↗

Grafts modulate dopamine transporters of the non-lesioned striatum.

The effect of intraventricular fetal mesencephalic grafts placed in the previously 6-hydroxydopamine (6-OHDA) lesioned striatum on the kinetics of [3H]dopamine (DA) uptake into striatal synaptosomes prepared from the non-lesioned (contralateral) striatum was studied in rats. Using WIN 35,065 as specific [3H]DA uptake inhibitor, the equilibrium dissociation constant (Km) of [3H]DA uptake into synaptosomes of the non-lesioned (contralateral) striatum did not differ between grafted and nongrafted controls 7 months after grafting. However, the maximal rate of specific [3H]DA uptake (Vmax) was markedly decreased in the non-lesioned striatum of grafted animals. This result indicates that fetal mesencephalic grafts reduce the [3H]DNA uptake in the non-lesioned (contralateral) striatum by reducing the number of functional DA transporters.

Analysis of Variance↗