TIME-COURSE OF MODIFICATIONS ELICITED BY RESERPINE ON THE DENSITY ANDMESSENGER-RNA SYNTHESIS OF THE VESICULAR MONOAMINE TRANSPORTER, AND ON THE DENSITY OF THE MEMBRANE DOPAMINE UPTAKE COMPLEX

The long-term effects of a unique injection of reserpine (5 mg/kg s.c. ) on the vesicular monoamine transporter and dopamine uptake complex h ave been investigated, in parallel with behavioral and neurochemical e ffects. Early after treatment, a dramatic decrease in locomotor activi ty, as well as a marked depletion in striatal dopamine (DA), associate d with a prominent enhancement in dopaminergic turnover were observed in reserpine-treated rats. From 2 to 60 days after reserpine injection , a recovery in locomotor activity occurred, in parallel with an incre ased DA content in the striatum, reaching about 50% of controls at day 60. At this time, the dopamine turnover was quite normal. The density of the dopamine uptake sites in the striatum, studied with H-3 GBR127 83, was unchanged after reserpine treatment at any time studied up to 60 days. By contrast, the density of binding sites for H-3 dihydrotetr abenazine (H-3 TBZOH), a marker for the vesicular monoamine transporte r, remained dramatically decreased in the striatum all over the time o f the study (> -90% of controls at day 2 and -80% at day 30 and 60). A lesser decrease (-60%) was observed in the substantia nigra pars comp acta (SNc), 2 and 30 days after reserpine treatment. This suggests tha t at least 60% of the vesicular monoamine transporter is sensitive to reserpine in this cell bodies region, indicating that this proportion of the transporter is integrated in functional vesicles, a prerequisit e for reserpine binding. On the other hand, in spite of profound modif ications of DA levels and neuronal activity, induced by a persistent b lockade of the vesicular uptake process, the density of mRNA encoding the vesicular monoamine transporter remained constant in the SNc from 2 to 60 days following reserpine injection. (C) 1995 Wiley-Liss, Inc.