Effects of cocaine on monoamine uptake as measured ex vivo.

The increase in extracellular dopamine (DA) following cocaine administration plays a major role in cocaine abuse. In vitro, cocaine binds to DA transporters (DAT) and blocks DA uptake. Moreover, cocaine can increase extracellular DA concentration as measured by in vivo neurochemical methods. The present study examined the effects of cocaine and other drugs on DA, NE and 5-HT uptake using an ex vivo assay. Rats were injected i.v. with saline or drug and sacrificed at various time points after injections. Brains were dissected for regional monoamine uptake studies ex vivo. In most brain regions, cocaine given in vivo blocked monoamine uptake as expected. [3H]DA uptake in nucleus accumbens was inhibited with an ED50=22.3 micromol/kg. Cocaine fully inhibited [3H]NE uptake (ED50=4.58 micromol/kg) in the occipital cortex and partially inhibited [3H]5-HT uptake (33% at 30 micromol/kg) in the midbrain. However, under the same conditions [3H]DA uptake in the striatum was not inhibited after injections of cocaine up to 56 micromol/kg. Although the mechanism for this discrepancy is unclear, DA binding and uptake sites may be distinct and/or there may be regional differences in DA transporters.