Genetic Deletion of Trace Amine 1 Receptors Reveals Their Role in Auto-Inhibiting the Actions of Ecstasy (MDMA)
Journal of Neuroscience November 23, 2011 Benjamin Di Cara, Roberto Maggio, Gabriella Aloisi et al. 97 citations
MDMA (ecstasy) activates trace amine-1 receptors (TA1Rs), which normally inhibit dopamine and serotonin release. In mice lacking TA1Rs, MDMA caused only hyperthermia (not the biphasic temperature response seen in normal mice), produced larger increases in dopamine levels in the striatum, frontal cortex, and nucleus accumbens, and led to greater locomotion that was blocked by haloperidol. Serotonin release was also amplified in TA1R-deficient mice. A TA1R agonist reduced the dopamine- and serotonin-releasing effects of another drug in normal mice but not in knockout mice. TA1Rs thus limit MDMA's neurochemical and behavioral effects, suggesting they play a regulatory role in the drug's actions.