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To assess whether a single dose of the SSRI escitalopram affects endogenous serotonin concentrations in serotonergic projection areas and in the raphe nuclei (RN), three cynomolgus monkeys and nine human subjects underwent PET examinations with [11C]AZ10419369 at baseline conditions and after escitalopram administration. In monkeys, the binding potential (BPND) was significantly lower post dose compared to baseline in dorsolateral prefrontal cortex, occipital cortex, thalamus, midbrain and RN (p &lt; 0.05). In humans, the BPND tended to decrease in RN post dose (p = 0.08). In all serotonergic projection areas, the BPND was conversely higher post dose compared to baseline. The increase was significant in a combined region of all projection areas (p = 0.01) and in occipital and temporal cortex (p &lt; 0.05). SSRIs are generally assumed to elevate endogenous serotonin concentrations in projection areas, evoking the antidepressant effect. In the present study, a single, clinically relevant, dose of escitalopram was found to decrease serotonin concentrations in serotonergic projection areas in humans. Hypothetically, desensitization of inhibitory serotonergic autoreceptors will cause the serotonin concentration in projection areas to increase over time with chronic administration. Thus, the findings in the present study might aid in understanding the mechanism of SSRIs' delayed onset of clinical effect.<\/jats:p>","DOI":"10.1017\/s1461145712001617","type":"journal-article","created":{"date-parts":[[2013,1,25]],"date-time":"2013-01-25T08:35:44Z","timestamp":1359102944000},"page":"1577-1586","source":"Crossref","is-referenced-by-count":84,"title":["Effect of a single dose of escitalopram on serotonin concentration in the non-human and human primate brain"],"prefix":"10.1093","volume":"16","author":[{"given":"Magdalena","family":"Nord","sequence":"first","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Center for Psychiatric Research, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sjoerd J.","family":"Finnema","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Center for Psychiatric Research, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christer","family":"Halldin","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Center for Psychiatric Research, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Farde","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Center for Psychiatric Research, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,8,1]]},"reference":[{"key":"2019101113491892400_ref1","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/0014-2999(92)90292-C","article-title":"Fluvoxamine preferentially increases extracellular 5-hydroxytryptamine in the raphe nuclei: an in vivo microdialysis study","volume":"229","author":"Bel","year":"1992","journal-title":"Eur J Pharmacol"},{"key":"2019101113491892400_ref2","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1002\/syn.890150310","article-title":"Chronic treatment with fluvoxamine increases extracellular serotonin in frontal cortex but not in raphe nuclei","volume":"15","author":"Bel","year":"1993","journal-title":"Synapse"},{"key":"2019101113491892400_ref3","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1056\/NEJMra073096","article-title":"Major depressive disorder","volume":"358","author":"Belmaker","year":"2008","journal-title":"N Engl J Med"},{"key":"2019101113491892400_ref4","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/00004728-198102000-00027","article-title":"Head fixation device for reproducible position alignment in transmission CT and positron emission tomography","volume":"5","author":"Bergstrom","year":"1981","journal-title":"J Comput Assist Tomogr"},{"key":"2019101113491892400_ref5","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1016\/j.clinbiochem.2009.05.006","article-title":"A rapid and reliable method for the quantitation of tricyclic antidepressants in serum using HPLC-MS\/MS","volume":"42","author":"Breaud","year":"2009","journal-title":"Clin Biochem"},{"key":"2019101113491892400_ref6","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.neuroimage.2005.09.052","article-title":"Increased serotonin receptor availability in human sleep: evidence from an [18F]MPPF PET study in narcolepsy","volume":"30","author":"Derry","year":"2006","journal-title":"Neuroimage"},{"key":"2019101113491892400_ref7","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1002\/syn.20780","article-title":"Fenfluramine-induced serotonin release decreases [(11)C]AZ10419369 binding to 5-HT(1B)-receptors in the primate brain","volume":"64","author":"Finnema","year":"2010","journal-title":"Synapse"},{"key":"2019101113491892400_ref8","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/jcbfm.2011.172","article-title":"Confirmation of fenfluramine effect on 5-HT(1B) receptor binding of [(11)C]AZ10419369 using an equilibrium approach","volume":"32","author":"Finnema","year":"2012","journal-title":"J Cereb Blood Flow Metab"},{"key":"2019101113491892400_ref9","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/0024-3205(94)00876-0","article-title":"Uptake inhibitors increase extracellular serotonin concentration measured by brain microdialysis","volume":"55","author":"Fuller","year":"1994","journal-title":"Life Sci"},{"key":"2019101113491892400_ref10","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/S0014-2999(98)00579-2","article-title":"Effect of fluoxetine on extracellular 5-hydroxytryptamine in rat brain. 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