The club drug MDMA (ecstasy) primarily causes serotonin release by reversing the serotonin transporter. This study in mice shows that blocking or removing the 5-HT2B receptor completely stops MDMA-induced hyperactivity and serotonin release in key brain regions (nucleus accumbens and ventral tegmental area). The 5-HT2B receptor acts presynaptically to regulate MDMA-stimulated serotonin release, a previously unknown role. These findings suggest that 5-HT2B receptor antagonists could be promising treatments for MDMA abuse.
The drug MDMA (ecstasy) produces its rewarding effects by causing the release of serotonin and dopamine in brain regions linked to reward. This study shows that the 5-HT(2B) receptor, a type of serotonin receptor, is essential for MDMA's reinforcing properties. Mice lacking the 5-HT(2B) receptor did not develop a preference for the location where they received MDMA (10 mg/kg) nor did they show behavioral sensitization. Blocking this receptor with an antagonist also prevented these effects in normal mice. However, at a higher dose (30 mg/kg), MDMA's effects were independent of serotonin and the 5-HT(2B) receptor, relying instead on dopamine. These findings highlight the dose-dependent role of serotonin-dopamine interactions in MDMA's addictive potential.