Voltammetric characterization of the effect of monoamine uptake inhibitors and releasers on dopamine and serotonin uptake in mouse caudate-putamen and substantia nigra slices.

Fast scan cyclic voltammetry is an electrochemical technique used to measure dynamics of transporter-mediated monoamine uptake in real time and provides a tool to evaluate the detailed effects of monoamine uptake inhibitors and releasers on dopamine and serotonin transporter function. We measured the effects of cocaine, methylphenidate, 2beta-propanoyl-3beta-(4tolyl) tropane (PTT), fluoxetine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), phentermine and fenfluramine on dopamine and serotonin uptake following electrically stimulated release in mouse caudate-putamen and substantia nigra pars reticulata slices. We determined rank orders of uptake inhibition effects based on two variables; increases in apparent K(m) for dopamine and serotonin uptake and inhibition constant (K(i)) values. For example, the rank order of uptake inhibition based on apparent K(m) values at the dopamine transporter was amphetamine>or=PTT>or=methylphenidate>>methamphetamine=phentermine=MDMA>cocaine>>fluoxetine=fenfluramine, and at the serotonin transporter was fluoxetine=methamphetamine=fenfluramine=MDMA > amphetamine=cocaine=PTT>or=methylphenidate>phentermine. Additionally, changes in electrically stimulated release were documented. This is the first study using voltammetry to measure the effects of a wide range of monoamine uptake inhibitors and releasers on dopamine and serotonin uptake in mouse brain slices. These studies also highlight methodological considerations for comparison of effects between heterogeneous brain regions.