Increased dopamine uptake in striatal synaptosomes after treatment of ratswith amantadine

The aim of the present study was to investigate the effect of short- and lo ng-term treatments with amantadine on the activity of the neuronal dopamine transporter (DAT) in the rat striatum. For this purpose, the [H-3]dopamine uptake was measured in striatal synaptosomes prepared from rats treated fo r 2, 7 and 14 days with amantadine (40 mg/kg; i.p.). After 7 days of treatm ent, amantadine increased the apparent V-max by 30% without modification of the apparent K-m of dopamine uptake whereas no change in these parameters was observed after 2 and 14 days treatment. Binding assays conducted with [ H-3]GBR-12935 on membranes prepared from animals treated with amantadine re vealed no difference in the density and the affinity of striatal DAT bindin g sites as compared to control. This indicates that the increased dopamine uptake was not reflecting a modification at the level of the DAT expression . The activity of the DAT is regulated by phosphorylation and one may propo se that ionotropic glutamate receptors present on presynaptic terminals dir ectly modulate this phosphorylation. An indirect mechanism would involve pr esynaptic dopamine receptors that control the activity of the DAT in respon se to the increased dopamine concentration in the synaptic cleft. (C) 2000 Elsevier Science B.V. All rights reserved.