5-HT2C receptors in the nucleus accumbens constrain the rewarding effects of MDMA.
bioRxiv : the preprint server for biology October 22, 2024 Matthew B Pomrenze, Sam Vaillancourt, Juliana S Salgado et al. 1 citation preprint
MDMA releases both dopamine and serotonin in the brain's reward center, the nucleus accumbens, but its strong serotonin release limits dopamine release and abuse potential. Using conditional knockout mice and direct brain infusions, the authors show that MDMA's serotonin release, acting through the serotonin transporter and 5-HT2C receptors, reduces the drug's reinforcing effects and conditioned place preference, while its prosocial effects are mediated by separate mechanisms. This platform predicts that (R)-MDMA, a novel entactogen, will have prosocial effects and low abuse potential.