Continuous cocaine induces persisting alterations in dopamine overflow in caudate following perfusion with a D1 agonist.

The present study examined whether exposure to 5 days of continuous cocaine in rats would produce any persisting alterations of the decrease in striatal dopamine (DA) overflow produced by local infusion of a D1 receptor agonist. Using a microdialysis probe in striatum, changes in DA, DA metabolites, and GABA were assessed 14 to 21 days following a 5-day continuous cocaine treatment. There were no differences in baseline levels of DA and it's metabolites. SKF 38393 (10(-6) infusion into the striatum decreased striatal DA levels in the controls and this effect was attenuated in cocaine-pretreated rats. This result, together with other observations, supports the hypothesis of a persistently altered D1-mediated negative feedback produced by previous exposure to continuous cocaine.