Estimation of striatal dopamine spillover and metabolism in vivo

Abstract

A microdialysis probe with an attached microinjection cannula was inserted into rat striatum. [3H]dopamine (or [14C]sucrose as a reference substance for diffusion) was infused via the cannula, with microdialysate sampled for concentrations of endogenous and [3H]-labeled dopamine and its metabolites. The calculated specific activities of the [3H]-labeled metabolites led to the conclusions that striatal extracellular dopamine undergoes inactivation mainly by extraneuronal but also by neuronal uptake and intracellular metabolism. Some of the dopamine taken up into nerve terminals slowly re-enters (spillover) the extracellular fluid unchanged. This spillover was calculated to be about 5 pmol/min. Destruction of dopaminergic terminals increases the turnover of vesicular stores in the surviving terminals, both by increased vesicular leakage and by increased release into the extracellular fluid.