title: Serotonin in cisternal cerebrospinal fluid of rhesus monkeys: basal levels and effects of sertraline administration.
abstract: 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.
authors.affiliation: Department of Child Psychiatry, Yale University School of Medicine, 230 S. Frontage Road, New Haven, CT 06510, USA. george.anderson@yale.edu
authors.forename: George M
authors.initials: GM
authors.lastname: Anderson
authors.forename: Allyson J
authors.initials: AJ
authors.lastname: Bennett
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Weld
authors.forename: Judy G
authors.initials: JG
authors.lastname: Pushkas
authors.forename: David M
authors.initials: DM
authors.lastname: Ocame
authors.forename: J Dee
authors.initials: JD
authors.lastname: Higley
mesh_terms: 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*
chemical_list: D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline