Springer OnlineHelp


Advanced search
AboutBrowseFavoritesTable Of Contents & Keyword AlertOrders LogOff


Publisher: Springer-Verlag Heidelberg
ISSN: 0033-3158 (Paper) 1432-2072 (Online)
DOI: 10.1007/s00213-004-2011-7
Issue: Online First

Original Investigation

Time course of the effects of the serotonin-selective reuptake inhibitor sertraline on central and peripheral serotonin neurochemistry in the rhesus monkey

George M. AndersonContact Information, Christina S. Barr2, Stephen Lindell2, Amy C. Durham2, Ilya Shifrovich1 and J. Dee Higley2

(1)  Departments of Child Psychiatry and Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA
(2)  Laboratory of Clinical Studies-Primate Unit, The National Institute of Alcohol Abuse & Alcoholism (NIAAA), Poolesville, MD, USA

Received: 11 June 2004  Accepted: 5 August 2004  Published online: 25 September 2004

Rationale  Fundamental questions remain regarding the actions of the selective serotonin reuptake inhibitors (SSRIs).
Objectives  To examine the time course of central and peripheral neurochemical effects of sertraline (SER) in non-human primates.
Methods  SER (20 mg/kg, p.o.) or placebo were administered daily for 4 weeks to two groups of six young adult male rhesus monkeys. Both groups received placebo during a 3-week baseline lead-in period and for 6 weeks after discontinuation. Blood and cisternal cerebrospinal fluid (cCSF) samples were obtained on days –21, –14, –7, 0, +3, +7, +14, +21, +28, +35 and +70.
Results  In animals receiving SER, mean (±SD) levels of cCSF serotonin (5-HT) increased from 38.6±9.0 pg/ml at baseline to 128±46.4 pg/ml during treatment (paired t=4.17, P=0.014). Concentrations of cCSF 5-HT were 290% of baseline on day 0 (+3 h), ranged from 260% to 436% of baseline during treatment, and returned to baseline 7 days after discontinuation. Levels of cCSF 5-hydroxyindoleacetic acid declined to 51±2.0% of baseline by day +3 and remained at similarly reduced levels during treatment. Plasma drug levels and decrements in platelet 5-HT were similar to those seen in patients.
Conclusions  SER rapidly and substantially increases cCSF levels of 5-HT in primates, the extent of elevation is relatively constant during prolonged administration, and values return to baseline shortly after discontinuation. The results suggest that response latency for SSRIs in depression is not due to gradually increasing brain extracellular fluid 5-HT levels and tend not to support theories that posit SSRI response latency as being due to autoreceptor desensitization, transporter downregulation, or drug accumulation.

Keywords  Serotonin - Cerebrospinal fluid - CSF - Rhesus monkey - Cisternal - Sertraline - Selective serotonin reuptake inhibitor - SSRI - 5-Hydroxyindoleacetic acid

Contact Information George M. Anderson
Email: george.anderson@yale.edu
Phone: +1-203-7854793
Fax: +1-203-7857611

The references of this article are secured to subscribers.

Previous article
Next article
Linking Options
You are not logged in.
The full text of this article is secured to subscribers. You or your institution may be subscribed to this publication.

If you are not subscribed, this publisher offers secure article or subscription sales from this site.

Please select 'Continue' to view your options for obtaining the full text of this article.

Frequently asked questions | General information on journals and books

Springer-Verlag Heidelberg  |  Tiergartenstr. 17  |  D-69121 Heidelberg  |  Germany  |   Privacy, Disclaimer, Terms and Conditions, © Copyright Information

Remote Address: • Server: MPWEB07
HTTP User Agent: Mozilla/4.0 (compatible; MSIE 6.0; Windows 98)