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Psychopharmacology (Berl). 2014 Apr;231(7):1409-16. doi: 10.1007/s00213-013-3329-9. Epub 2013 Nov 6.

Sertraline effects on cerebrospinal fluid monoamines and species-typical socioemotional behavior of female cynomolgus monkeys.

Author information

1
Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1040, USA, cshively@wakehealth.edu.

Abstract

RATIONALE:

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 % (pā€‰<ā€‰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.

PMID:
24193371
PMCID:
PMC3954916
DOI:
10.1007/s00213-013-3329-9
[Indexed for MEDLINE]
Free PMC Article

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