Sex differential effect of dexmedetomidine on fear memory extinction and anxiety behavior in adolescent rats

Exposure to stressful stimuli, including fear and anxiety, modulates the central noradrenergic system. Dexmedetomidine is a commonly used α2-adrenoreceptor agonist. Because the effect of fear acquisition varies between sexes, the present study was designed to investigate sex-related differences in the effects of dexmedetomidine on fear memory and anxiety-like behavior. We conducted a fear test and an elevated plus maze test in 6-8-week-old male and female rats. Two doses of dexmedetomidine (20 and 40 μg/kg) were injected intraperitoneally three times at 24 h intervals after the tests: after fear expression, extinction 1, and extinction 2. The repeated administration of dexmedetomidine showed significant acceleration of fear memory extinction in female rats but not in male rats; the effect increased proportionally to concentrations of dexmedetomidine. Compared to male rats, female rats treated with both concentrations of dexmedetomidine showed significant anxiolytic behavior after 1 week. Dexmedetomidine accelerated the fear memory extinction and reduced anxiety; it was more effective in female rats than in male rats. Our results suggest that dexmedetomidine may exert protective effects against fear-related and anxiety-like behaviors in rats with fear memory after repeated administration, and the sex-specific effects of dexmedetomidine should be considered.