RESUMO
BACKGROUND: Despite observed sex differences in the prevalence of stress-related psychiatric conditions, most preclinical and translational studies have only included male subjects. Therefore, it has not been possible to effectively assess how sex interacts with other psychosocial risk factors to impact the etiology and maintenance of stress-related psychopathology. One psychosocial factor that interacts with sex to impact risk for stress-related behavioral and physiological deficits is social dominance. The current study was designed to assess sex differences in the effects of social status on socioemotional behavior and serotonin neurochemistry in socially housed rhesus monkeys. We hypothesized that sex and social status interact to influence socioemotional behaviors as well as serotonin 1A receptor binding potential (5HT1AR-BP) in regions of interest (ROIs) implicated in socioemotional behavior. METHODS: Behavioral observations were conducted in gonadally intact adult female (n = 14) and male (n = 13) rhesus monkeys. 5HT1AR-BP was assessed via positron emission tomography using 4-(2'-Methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p[18F]fluorobenzamido]ethylpiperazine ([18F]MPPF). RESULTS: Aggression emitted was greater in dominant compared to subordinate animals, regardless of sex. Submission emitted was significantly greater in subordinate versus dominant animals and greater in females than males. Affiliative behaviors emitted were not impacted by sex, status, or their interaction. Anxiety-like behavior emitted was significantly greater in females than in males regardless of social status. Hypothalamic 5HT1AR-BP was significantly greater in females than in males, regardless of social status. 5HT1AR-BP in the dentate gyrus of the hippocampus was significantly impacted by a sex by status interaction whereby 5HT1AR-BP in the dentate gyrus was greater in dominant compared to subordinate females but was not different between dominant and subordinate males. There were no effects of sex, status, or their interaction on 5HT1AR-BP in the DRN and in the regions of the PFC studied. CONCLUSIONS: These data have important implications for the treatment of stress-related behavioral health outcomes, as they suggest that sex and social status are important factors to consider in the context of serotonergic drug efficacy.
Females are more likely to suffer from stress-related conditions that impact socioemotional behavior compared to males. One thing that influences how sex impacts stress-related health problems is social dominance. We examined whether there are sex differences in the effects of social dominance on socioemotional behavior in socially housed rhesus monkeys. Because the neurotransmitter serotonin is important for socioemotional behavior, we also looked at the levels of the 5HT1AR receptor using neuroimaging. Aggression was greater in dominant compared to subordinate animals, and submission was significantly greater in subordinate versus dominant animals and greater in females than males. Anxiety and levels of 5HT1AR in the hypothalamus were significantly greater in females than in males. 5HT1AR in the hippocampus was greater in dominant compared to subordinate females but was not different between dominant and subordinate males. Overall, these data are important for the treatment of stress-related behavioral health outcomes because suggest that sex and social dominance are important factors to consider in the context of how effective drugs targeting the serotonin system are for treating stress-related behavioral health conditions.
