title: Sertraline effects on cerebrospinal fluid monoamines and species-typical socioemotional behavior of female cynomolgus monkeys.
abstract: BACKGROUND
  Although widely prescribed, little is known about the effects of selective serotonin reuptake inhibitors (SSRIs) on social behavior and cerebrospinal fluid (CSF) monoamines in female primates.
  
  
  OBJECTIVE
  The objective of this study was to determine the effects of sertraline on agonistic and affiliative behavior.
  
  
  METHODS
  Twenty-one adult female cynomolgus monkeys were housed in small, stable social groups, trained to participate in oral dosing, and began a 5-week cumulative dose-response study. Serial doses of 0, 5, 10, 15, and 20 mg/kg of sertraline were administered orally for 1 week each. Behavior was recorded daily during 10-min observations before and 4 h after dosing. On the seventh day of dosing, circulating sertraline/desmethylsertraline and CSF monoamines/metabolites were determined 4 h after the last dose.
  
  
  RESULTS
  At 20 mg/kg, circulating sertraline/desmethylsertraline was in the therapeutic range. CSF 5-hydroxyindole acetic acid decreased by 33 % (p < 0.05). Overall aggression, submission, locomotion, and time alone decreased, whereas affiliative behaviors (body contact, grooming) increased (all p values <0.05). Effects of sertraline on aggression and submission were social status-dependent, reducing aggression in dominants and submission in subordinates.
  
  
  CONCLUSIONS
  A clinically relevant oral dose of sertraline resulted in CSF metabolite changes similar to those observed in patients and altered the socioemotional behavior of female monkeys. Changes in CSF 5-HT and dopamine are novel observations that may be sex-specific. The robust effects of sertraline on aggression and affiliation may explain the efficacy of SSRIs on a range of human behavioral pathologies that share the characteristics of increased aggression and decreased sociality.
authors.affiliation: Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1040, USA, cshively@wakehealth.edu.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Shively
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Register
authors.forename: J Dee
authors.initials: JD
authors.lastname: Higley
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Willard
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000134:cerebrospinal fluid* / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006608:Hierarchy, Social; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid / Q000378:metabolism; D008252:Macaca fascicularis; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D020280:Sertraline / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D012919:Social Behavior
chemical_list: D015306:Biogenic Monoamines; D006897:Hydroxyindoleacetic Acid; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline