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. Local perfusion of 10 microM serotonin (5-hydroxytryptamine, 5-HT) increased basal dopamine levels approximately 7-fold (664 +/- 79%, 813 +/- 104% and 669 +/- 22%, n = 6, P < 0.0001) in saline-treated controls, whereas 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 returned 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 effectiveness of 5-HT on striatal dopaminergic activity.