Sex-specific effects of endocannabinoid hydrolysis inhibition on fear memory dynamics

Fear extinction is an essential process for recovery from traumatic events. Endocannabinoids are importantly involved in modulating fear extinction and the recruitment of fear coping strategies in male rodents; however, little is understood about this regulation in females. Preclinical studies show that females prefer active fear coping strategies (darting), while males predominately exhibit passive fear responses (freezing). We examined potential sex differences of endocannabinoid modulation of fear memory extinction and fear coping responses in rats. We found that boosting endocannabinoid anandamide levels increased freezing and diminished darting in females to levels comparable to males, in early extinction learning and recall.