title: Changes in human in vivo serotonin and dopamine transporter availabilities during chronic antidepressant administration.
abstract: Few studies have demonstrated in vivo alterations of human serotonin and dopamine transporters (SERTS and DATS) during antidepressant treatment. The current study measured these transporter availabilities with [(123)I]beta-CIT single photon emission computed tomography (SPECT) during administration of selective serotonin reuptake inhibitors (SSRIs) or a non-SSRI, bupropion. A total of 17 healthy human subjects were randomly assigned to two different treatment protocols: (1). citalopram (40 mg/day) followed by augmentation with bupropion (100 mg/day) or (2). bupropion (100-200 mg/day) for 16 days. Citalopram significantly inhibited [(123)I]beta-CIT binding to SERT in brainstem (51.4%) and diencephalon (39.4%) after 8 days of administration, which was similarly observed after 16 days. In contrast, citalopram significantly increased striatal DAT binding by 15-17% after 8 and 16 days of administration. Bupropion and its augmentation to citalopram did not have a significant effect on DAT or SERT. In 10 depressed patients who were treated with paroxetine (20 mg/day), a similar increase in DAT and inhibition of SERT were observed during 6 weeks treatment. The results demonstrated the inhibition of SERT by SSRI in human in vivo during the chronic treatment and, unexpectedly, an elevation of DAT. This apparent SSRI-induced modulation of the dopamine system may be associated with the side effects of these agents, including sexual dysfunction.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. akira.kugaya@yale.edu
authors.forename: Akira
authors.initials: A
authors.lastname: Kugaya
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Seneca
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Snyder
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Williams
authors.forename: Robert T
authors.initials: RT
authors.lastname: Malison
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: John P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: Robert B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000494:pharmacology*; D016642:Bupropion / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D016642:Bupropion; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493214:SLC6A3 protein, human; C493230:SLC6A4 protein, human