Repeated exposure to methylenedioxymethamphetamine (MDMA) alters nucleus accumbens neuronal responses to dopamine and serotonin.

The purpose of this experiment was to investigate the effects of repeated exposure to methylenedioxymethamphetamine (MDMA) on responses of neurons in the nucleus accumbens of anesthetized rats to microiontophoretically-applied dopamine and serotonin. In tests conducted 1-4 days or 9-15 days following the last injection of MDMA (20 mg/kg, s.c., twice daily for 4 days), the inhibitory effects of both dopamine and serotonin on glutamate-evoked firing of nucleus accumbens cells were significantly attenuated compared to effects in control rats that were pretreated with saline injections. The inhibitory effect of the D1 receptor agonist SKF38393 was also significantly attenuated in the MDMA-pretreated rats. In contrast, the amount of inhibition of glutamate-evoked firing produced by application of GABA did not significantly differ between the MDMA-pretreated and the saline-pretreated rats. The neurotoxicity of the MDMA treatment regimen was confirmed by demonstrating that 3H-paroxetine binding was significantly decreased in the medial prefrontal cortex and the nucleus accumbens of the MDMA-pretreated rats. The mechanisms that produce the attenuated inhibitory responses to dopamine and serotonin following repeated injections of MDMA are not known. However, the results of these experiments indicate that repeated MDMA administration induces long-lasting changes in dopaminergic as well as serotonergic neurotransmission in the nucleus accumbens.