Nonhuman primates, females, SSRI, sertraline, CSF, social and emotional behavior


Rationale—Although widely prescribed, little is known about selective serotonin reuptake inhibitors (SSRIs) effects on social behavior and cerebrospinal fluid (CSF) monoamines in female primates.

Objective—To determine the effects of sertraline on agonistic and affiliative behavior.

Methods—21 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 one week each. Behavior was recorded daily during 10-minute observations before and 4 hours after dosing. On the 7th day of dosing, circulating sertraline/desmethylsertraline and CSF monoamines/metabolites were determined 4 hours after the last dose.

Results—At 20 mg/kg, circulating sertraline/desmethylsertraline was in the therapeutic range. CSF 5-hydroxyindole acetic acid decreased 33% (p

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.

Original Publication Citation

Shively CA, Register TC, Higley JD, Willard SL. Sertraline effects on cerebrospinal fluid monoamines and species-typical socioemotional behavior of female cynomolgus monkeys. Psychopharmacology (Berl). 2014 Apr;231(7):1409-16. doi: 10.1007/s00213-013-3329-9. Epub 2013 Nov 6. PMID: 24193371; PMCID: PMC3954916.

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Peer-Reviewed Article

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Psychopharmacology (Berl)




Family, Home, and Social Sciences



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Full Professor

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