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 % (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.
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 % (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: George M Anderson; Christina S Barr; Stephen Lindell; Amy C Durham; Ilya Shifrovich; J Dee Higley Journal: Psychopharmacology (Berl) Date: 2004-09-25 Impact factor: 4.530
Authors: Deborah S Moskowitz; Gilbert Pinard; David C Zuroff; Lawrence Annable; Simon N Young Journal: Adv Exp Med Biol Date: 2003 Impact factor: 2.622
Authors: Jamie N Justice; Marnie G Silverstein-Metzler; Beth Uberseder; Susan E Appt; Thomas B Clarkson; Thomas C Register; Stephen B Kritchevsky; Carol A Shively Journal: Geroscience Date: 2017-10-28 Impact factor: 7.713
Authors: Elizabeth G Pitts; Adelaide R Minerva; Erika B Chandler; Jordan N Kohn; Meghan T Logun; Agnieszka Sulima; Kenner C Rice; Leonard L Howell Journal: Neuropsychopharmacology Date: 2017-04-20 Impact factor: 7.853
Authors: Stephanie L Willard; Beth Uberseder; Ashlee Clark; James B Daunais; Warwick D Johnston; David Neely; Adreanna Massey; Jeff D Williamson; Robert A Kraft; J Daniel Bourland; Sara R Jones; Carol A Shively Journal: Neuropharmacology Date: 2015-06-24 Impact factor: 5.250
Authors: Marnie G Silverstein-Metzler; Jamie N Justice; Susan E Appt; Leanne Groban; Dalane W Kitzman; John Jeffrey Carr; Thomas C Register; Carol A Shively Journal: Menopause Date: 2017-10 Impact factor: 2.953
Authors: Marnie G Silverstein-Metzler; Carol A Shively; Thomas B Clarkson; Susan E Appt; J Jeffrey Carr; Stephen B Kritchevsky; Sara R Jones; Thomas C Register Journal: Psychoneuroendocrinology Date: 2016-02-21 Impact factor: 4.905