Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse

Methylenedioxymethamphetamine (MDMA) is an amphetamine analogue that preferentially stimulates the release of serotonin (5HT) and results in relatively small increases synaptic dopamine (DA). The ratio drug-stimulated DA, relative to 5HT, predicts abuse liability; drugs with higher DA:5HT ratios are more likely be abused. Nonetheless, MDMA a drug misused. Clinical preclinical studies have suggested repeated exposure produces neuroadaptive responses both 5HT DA neurotransmission might explain development maintenance self-administration some laboratory animals substance use disorder humans. In this paper, we describe research has demonstrated inhibitory effect on acquisition critical role animals. We then circuitry receptors positioned modulate activity review limited effects these receptor mechanisms.