REPEATED COCAINE EXPOSURE ATTENUATES THE ABILITY OF 5-HYDROXYTRYPTAMINE TO RELEASE STRIATAL DOPAMINE IN-VIVO

Cocaine was administered repeatedly to rats and striatal microdialysis performed 1, 7, 14, or 21 days after the last cocaine injection. Loca l perfusion of 10 mu M serotonin (5-hydroxytryptamine, 5-HT) increased basal dopamine levels approximately 7-fold (664 +/- 79%, 813 +/- 104% and 669 +/- 62%, n = 6, P < 0.0001) in saline-treated controls, where as in cocaine-treated animals the effect was significantly attenuated (432 +/- 55%, 465 +/- 61% and 497 +/- 48% n = 6-10, P < 0.03) at 1, 7 and 14 days of withdrawal. The 5-HT effect on dopamine release returne d to control levels 21 days after cocaine exposure and was not altered by acute cocaine treatment (30 mg/kg, i.p., 24 h prior). The results suggest that repeated cocaine administration attenuates the effectiven ess of 5-HT on striatal dopaminergic activity.