In this study, we examined the ability of a single injection of cocaine (20 mg/kg, i.p.) to augment extracellular dopamine levels in the nucleus accumbens two weeks after pretreating rats with either saline (1 ml/kg, i.p.) or the serotonin neurotoxin 3,4-methylenedioxymethamphetamine (20 mg/kg, s.c., twice daily for 4 days). The level of dopamine in the nucleus accumbens was measured using in vivo microdialysis. Cocaine produced a 400% increase in extracellular nucleus accumbens dopamine levels in control rats, whereas in 3,4-methylenedioxymethamphetamine treated rats the increase produced by cocaine was 800%, which was significantly different from controls. This suggests that 3,4-methylenedioxymethamphetamine, a relatively common drug of abuse, may alter subsequent vulnerability to cocaine dependence and abuse.