Serotonin in cisternal cerebrospinal fluid of rhesus monkeys: basal levels and effects of sertraline administration.
BACKGROUND
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.
Anderson
George M
GM
Department of Child Psychiatry, Yale University School of Medicine, 230 S. Frontage Road, New Haven, CT 06510, USA. george.anderson@yale.edu
Bennett
Allyson J
AJ
Weld
Katherine P
KP
Pushkas
Judy G
JG
Ocame
David M
DM
Higley
J Dee
JD
D000818:Animals; D008253:Macaca mulatta; D008297:Male; D017551:Microdialysis; D012701:Serotonin / Q000134:cerebrospinal fluid*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline / Q000494:pharmacology*
D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline