BRAIN SEROTONIN TRANSPORTER IN ECSTASY AND MDA USERS

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DESCRIPTION (provided by applicant): Background. Animal data indicate that the widely used illicit drug ecstasy (mdma) and its more potent metabolite, mda (previously known as the "love drug"), can damage brain serotonin neurones. However, results of limited in vivo neuroimaging studies attempting to measure levels of brain serotonin markers in human drug users are uncertain because of problems in experimental design and in validity and reliability of the radiolabeled probes used to assess serotonin neurone integrity. Broad objective. Our broad objective is to establish the extent to which ecstasy and mda "harms" human brain. Specific Aim, Hypothesis, and Design. Our major SPECIFIC AIM is to establish by PET (positron emission tomography) neuroimaging whether levels of a key component of serotonin neurones, the serotonin transporter (SERT), as inferred from binding of our recently developed probe, [11C]-DASB, are reduced in brain of chronic users of ecstasy and in users of mda as compared with those in a matched control group. Our investigation includes the use of forensic hair analysis to prove unequivocally chronic use of ecstasy/mda, and utilisation of a new SERT radiolabeled probe, developed by our PET centre, which is free of the validity/reliability problems associated with previous radiotracers. Health relevance. The obtained data will provide useful information on the question of whether ecstasy and mda (a drug which we believe will increasingly become more popular) might compromise function of brain serotonin neurones in humans. More broadly, our data will help define the contribution of different neuroanatomical components of the brain serotonin system to human behavior.