Sex Differences in Behavioral Response to Social Stress

Anxiety disorder diagnoses among females are about two times more prevalent than they are for males. Intriguingly however, suicide completion rates are higher among males. From this discrepancy arises questions regarding the development of stress-related behaviors, and the associated differences between the sexes. Neurocircuits involving orexin are known to play roles in the formation of anxious and depressive behaviors. The Stress Alternatives Model (SAM) protocol produces behaviors revealing adaptive and maladaptive phenotypes. The SAM consists of a four-day program in which two different types of mice, smaller test mice and novel larger, aggressive mice, are allowed to interact inside an oval open field arena for five minutes. On opposite sides of the arena are small escape tunnels only the smaller mouse can utilize. Before each session, test mice are fear conditioned to a tone prior to social interaction. By the end of the second day of the SAM, animals diverge into maladaptive (Stay) and adaptive (Escape) phenotypes. Females respond to aggression by exhibiting active avoidance (Escape) far more frequently than males. Additionally, females, when escaping, do so more rapidly than males. Although the female response is different, the amount of aggression received is exactly the same as the aggression received by a test male. Females also pay more attention to the escape route than males, and show reduced fear conditioning. After the SAM, mice are exposed to the Social Interaction/Preference (SIP) test in which both males and females exhibit increased resilience upon orexin 2 receptor agonist treatment. In both sexes, these behavioral responses are regulated by orexin 2 receptor activity