Sertraline effects on cerebrospinal fluid monoamines and species-typical socioemotional behavior of female cynomolgus monkeys
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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.
The objective of this study was to determine the effects of sertraline on agonistic and affiliative behavior.
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.
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.
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.
KeywordsNonhuman primates Females SSRI Sertraline CSF Social and emotional behavior
This work was supported by the National Institutes of Health RO1HL087103 and R21MH086731 (to CAS). We are grateful to Matthew McMullin and NMS Labs for his help with the sertraline and desmethylsertraline analyses. All procedures involving primates were conducted using protocols approved by the Institutional Animal Care and Use Committee of Wake Forest University and were in compliance with all institutional, state, and federal laws for the usage of primates in laboratory settings.
Conflict of interest
Drs. Shively, Register, Higley, and Willard reported no biomedical financial interests or potential conflicts of interest.
- Amaral D, Lavenex P (2007) Hippocampal neuroanatomy. In: Anderson P, Morris R, Amaral D, Bliss T, O'Keefe J (eds) The hippocampus book. Oxford University Press, New York, pp 37–114Google Scholar
- Pratt LA, Brody DJ, Gu Q (2011) Antidepressant use in persons aged 12 and over: United States, 2005–2008. NCHS data brief, no. 76. National Center for Health Statistics, HyattsvilleGoogle Scholar
- Reis M, Aberg-Wistedt A, Agren H, Höglund P, Akerblad AC, Bengtsson F (2004) Serum disposition of sertraline, N-desmethylsertraline and paroxetine: a pharmacokinetic evaluation of repeated drug concentration measurements during 6 months of treatment for major depression. Hum Psychopharmacol 19(5):283–291PubMedCrossRefGoogle Scholar
- Stroud FC, Appt SE, Wilson ME, Franke AA, Adams MR, Kaplan JR (2006) Concentrations of isoflavones in macaques consuming standard laboratory monkey diet. Am Assoc Lab Anim Sci 45(4):20–23Google Scholar