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Fluoxetine Administered to Juvenile Monkeys: Effects on the Serotonin Transporter and Behavior

 Stal Saurav Shrestha  ;  Eric E. Nelson  ;  Jeih-San Liow  ;  Robert Gladding  ;  Chul Hyoung Lyoo  ;  Pam L. Noble  ;  Cheryl Morse  ;  Ioline D. Henter  ;  Jeremy Kruger  ;  Bo Zhang  ;  Stephen J. Suomi  ;  Per Svenningsson  ;  Victor W. Pike  ;  James T. Winslow  ;  Ellen Leibenluft  ;  Daniel S. Pine  ;  Robert B. Innis 
 AMERICAN JOURNAL OF PSYCHIATRY, Vol.171(3) : 323-331, 2014 
Journal Title
Issue Date
Age Factors ; Animals ; Fluoxetine/pharmacology* ; Functional Neuroimaging ; Hippocampus/diagnostic imaging ; Hippocampus/metabolism* ; Interpersonal Relations* ; Macaca mulatta ; Male ; Maternal Deprivation* ; Neocortex/diagnostic imaging ; Neocortex/drug effects ; Neocortex/metabolism* ; Radionuclide Imaging ; Receptor, Serotonin, 5-HT1A/metabolism ; Serotonin Plasma Membrane Transport Proteins/metabolism* ; Serotonin Uptake Inhibitors/pharmacology ; Up-Regulation
OBJECTIVE: This study examined the long-term effects of fluoxetine administered to juvenile rhesus monkeys who, as young adults, were imaged with positron emission tomography for two serotonergic markers: serotonin transporter (SERT) and serotonin 1A (5-HT1A) receptor. An equal number of monkeys separated from their mothers at birth-an animal model of human childhood stress-were also studied. METHOD: At birth, 32 male rhesus monkeys were randomly assigned to either maternal separation or normal rearing conditions. At age 2, half (N=8) of each group was randomly assigned to fluoxetine (3 mg/kg) or placebo for 1 year. To eliminate the confounding effects of residual drug in the brain, monkeys were scanned at least 1.5 years after drug discontinuation. Social interactions were assessed both during and after drug administration. RESULTS: Fluoxetine persistently upregulated SERT, but not 5-HT1A receptors, in both the neocortex and the hippocampus. Whole-brain voxel-wise analysis revealed that fluoxetine had a significant effect in the lateral temporal and cingulate cortices. In contrast, neither maternal separation by itself nor the rearing-by-drug interaction was significant for either marker. Fluoxetine had no significant effect on the behavioral measures. CONCLUSIONS: Fluoxetine administered to juvenile monkeys upregulates SERT into young adulthood. Implications regarding the efficacy or potential adverse effects of SSRIs in patients cannot be directly drawn from this study. Its purpose was to investigate effects of SSRIs on brain development in nonhuman primates using an experimental approach that randomly assigned long-term SSRI treatment or placebo.
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1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Lyoo, Chul Hyoung(류철형) ORCID logo https://orcid.org/0000-0003-2231-672X
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