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- Title
Serotonin in cisternal cerebrospinal fluid of rhesus monkeys: basal levels and effects of sertraline administration.
- Authors
Anderson, George M.; Bennett, Allyson J.; Weld, Katherine P.; Pushkas, Judy G.; Ocame, David M.; Higley, Dee J.
- Abstract
Rationale: Studies of rodents suggest that extracellular fluid and cerebrospinal fluid (CSF) serotonin (5-HT) concentrations provide a better index of released 5-HT than the frequently obtained measure of CSF 5-hydroxyindoleacetic acid (5-HIAA). The measurement of cisternal CSF 5-HT levels in the monkey might offer a method of assessing the effects of agents and actions on central 5-HT functioning in primate brain. Objective: To address methodological issues related to the determination of monkey cisternal CSF 5-HT and to examine the effects of a selective serotonin reuptake inhibitor (SSRI) on the measure. Methods: Monkey CSF was obtained by cisternal puncture and 5-HT levels determined by high performance liquid chromatography, after screening for blood contamination. Results: When blood contamination was minimized, a mean (±SD) basal concentration of cisternal CSF 5-HT 87±36 pg/ml (n=13) was observed. Good longitudinal stability (variances of 16 and 20%) of CSF 5-HT was demonstrated in two monkeys sampled over a 3-month period. A two-fold increase in CSF 5-HT was seen in seven animals treated with the SSRI sertraline (20 mg/kg PO, mean treatment period of 12 days): pre- and post-drug 5-HT concentrations were 85±39 and 162±53 pg/ml (P=0.0007); in contrast, levels of 5-HIAA decreased from 40.0±5.7 to 20.4±2.2 ng/ml (P=0.0001). Conclusions: The measurement of monkey cisternal CSF 5-HT appears to provide a useful index of central 5-HT release. Initial results tend to support a role for increased extracellular 5-HT in the mechanism of action of chronically administered SSRIs.
- Subjects
EXTRACELLULAR fluid; CEREBROSPINAL fluid; SEROTONIN; RHESUS monkeys; DRUGS
- Publication
Psychopharmacology, 2002, Vol 161, Issue 1, p95
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-002-1034-1