65 A further study in 10 ecstasy users also demonstrated reduced

65 A further study in 10 ecstasy users also demonstrated reduced cortical SERT availability using SPECT and the SERT ligand β-CIT66 However, correlations between the SERT availability results, cumulative ecstasy consumption, and length of abstinence periods suggested a temporary occupation or downregulation of the binding site rather than structural

neurotoxic damage.66 Since then there has been some debate on the validity of SPECT and PET techniques with SERT ligands in measuring MDMA-related neurotoxicity and on Inhibitors,research,lifescience,medical additional subject-related methodological problems of these early studies. Nevertheless, all but one more recent studies Inhibitors,research,lifescience,medical with refined methods67 and larger samples (up to 61 current and former users68) confirmed reduced SERT availability at least in female current users with a relatively heavy use pattern (>50 pills),58-68-72 and only one small study with 12 former MDMA users was negative.73 All in all, alterations were less pronounced

in male users, and were absent in former users following abstinence from MDMA use of at least 12 months. A small longitudinal study with two follow-up (+)Microbiology inhibitor McN5652-PET examinations confirmed the reversibility of alterations of SERT availability with a decrease in the intensity of MDMA Inhibitors,research,lifescience,medical consumption.74 In summary, these studies indicate that women may be more susceptible to MDMAinduced alterations of the serotonergic system than men, and, in addition, they suggest at least some degree of recovery of the assumed

serotonergic lesion following abstinence. Inhibitors,research,lifescience,medical Interestingly, another SPECT study with the 5-HT2A receptor ligand [123I]-”type”:”entrez-nucleotide”,”attrs”:”text”:”R91150″,”term_id”:”958690″,”term_text”:”R91150″R91150 Inhibitors,research,lifescience,medical demonstrated reduced cortical binding in current ecstasy users with short-term abstinence and increased binding in former users who had not used ecstasy for an average of 5 months.75 This pattern is in line with animal data showing temporary (up to 1 month) downregulation of postsynaptic 5-HT2 receptors resulting from high synaptic 5-HT concentration after administration of MDMA, and long-lasting Phosphoprotein phosphatase upregulation of the same postsynaptic receptors following widespread presynaptic damage of serotonergic neurons leading to 5-HT depletion.76-77 Hence, unlike the SERT data, postsynaptic receptor data suggest that alterations of serotonergic systems may persist over long periods of time in abstinent MDMA users. Such subtle residual changes could be functionally important, and might contribute to clinical or subclinical alterations of psychological well-being and behavior of ecstasy users. Serotonin-related functions The neuromodulator 5-1 IT is involved in several functional systems of the CNS.

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