Role of 5-HT2A Receptors in MDMA induced Behavior

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DESCRIPTION: (Provided by Applicant): Abuse of the substituted amphetamine 3,4-Methylenedioxymethamphetamine (MDMA) has rapidly increased in recent years, particularly among adolescents. Users report that MDMA elevates mood and confidence and increases connectedness with others. However, MDMA has also been shown to produce undesirable alterations in mood, sleep, memory, and thermoregulation. The exact mechanisms of action for MDMA are unknown, but are thought to be mediated partly through MDMA-induced serotonin release via reversal of the serotonin transporter. Since serotonin release is important in mediating the effects of MDMA, our lab has focused on determining the role of specific serotonin receptors in the behavioral effects of MDMA. Preliminary data suggest that activation of the 5-HT2A receptor is important in generating hyperlocomotor activity elicited by MDMA, and the literature suggests that serotonin plays a role in the generation of MDMA-induced conditioned place preference (CPP). Both CPP and locomotor activity are generated by activation of the mesoaccumbens dopamine pathway. Therefore, the purpose of this proposal is to determine the involvement of 5-HT2A receptors in the hyperlocomotive and conditioned stimulus effects of MDMA.