The effects of fluoxetine on socioemotional behavior in female rhesus monkeys is influenced by social status
Authors: Wakeford Alison GP , Huhman Kim L , Jones Sara R , Locke Jason , Wilson Mark , Albers H. Elliott , Michopoulos Vasiliki 
Published: June 2021

BackgroundChronic adverse social experience is a major environmental variable linked to multiple psychiatric disorders. The use of social subordination in nonhuman primates represents a translational model of chronic psychosocial stress. While social dominance is associated with a resistance to a range of stressors and social subordination produces stress‐susceptible phenotypes, the neural mechanisms that underlie status‐induced differences in susceptibility remain unclear. The current study assessed the effects of increasing serotonin (5HT) activity by administering fluoxetine on rates of socioemotional behavior (including agonistic, affiliative, and anxiety‐like behaviors) in female rhesus monkeys. We hypothesized that fluoxetine would increase rates of aggression in dominant but not subordinate animals.MethodsSubjects were gonadally intact adult female rhesus monkeys (n=14) housed in small social groups of four to six females each (6 dominant and 8 subordinate females). Using a counterbalanced design, subjects received both a 14‐day treatment with fluoxetine (SC dose of 2.8 mg/kg/day) and vehicle (50% polyethylene glycol in sterile saline) separated by a three‐week washout period. Behavioral observations were collected every two days using a standard monkey ethogram during each treatment, and CSF samples were collected at the end of each treatment for assessment of central 5‐hydroxyindoleacetic (5HIAA).ResultsThe amount of aggression directed at group mates was influenced by a status by treatment interaction (p=0.05, η2=0.27), with fluoxetine enhancing aggression in dominant females and decreasing aggression in subordinate females. As expected, subordinate females emitted significantly higher rates of submission behavior than did dominant females and this was unaffected by treatment (p=0.001). Affiliation emitted towards others was influenced by a status by treatment interaction (p=0.05, η2=0.27), as fluoxetine treatment decreased affiliation emitted in dominant females and increased it in subordinates. Anxiety‐like behavior was also influenced by a status by treatment interaction (p=0.011), as anxiety‐like behaviors were reduced only in subordinate females by fluoxetine treatment (p=0.012). CSF 5HIAA concentrations were reduced by fluoxetine (p<0.001) regardless of social status.ConclusionThe data show that increased 5HT activity following fluoxetine treatment in female monkeys alters socioemotional behavior in a status‐dependent manner. Notably, subordinate females are less aggressive and more affiliative during fluoxetine treatment. Future studies include determining whether these effects of fluoxetine are sex dependent and whether subordinate males respond similarly to subordinate females.Support or Funding InformationThis research was supported by an NIMH grant MH110212.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.