MDMA increases extracellular dopamine and serotonin in the striatum and prefrontal cortex of mice. In mice lacking both dopamine and serotonin transporters, the dopamine increase in the striatum is absent, while the serotonin increase is greatly reduced. In the prefrontal cortex, MDMA raises dopamine levels regardless of transporter knockout. These findings confirm that MDMA acts on both the dopamine and serotonin transporters to elevate these neurotransmitters.
The hallucinogenic tryptamine analogue 5-MeO-DIPT decreases extracellular serotonin in the striatum but not in the prefrontal cortex of mice. In mice lacking the serotonin transporter, 5-MeO-DIPT does not affect serotonin levels, indicating its action depends on that transporter. When a 5-HT1A receptor antagonist is present, 5-MeO-DIPT substantially increases serotonin, suggesting the drug's serotonin reuptake inhibition is masked by its concurrent activation of 5-HT1A receptors. 5-MeO-DIPT also dose-dependently increases extracellular dopamine in the prefrontal cortex regardless of serotonin transporter presence, an effect not blocked by the 5-HT1A antagonist. Thus, 5-MeO-DIPT dually acts on the serotonin transporter and 5-HT1A receptors, limiting serotonin elevation while independently raising dopamine in the prefrontal cortex.