Editorial

Sex differences in neurological and psychiatric disorders

Understanding sex differences in behavioral and molecular effects of stress has important implications for understanding the vulnerability to chronic psychiatric disorders associated with stress response circuitry. The amygdala is critical for emotional learning and generating behavioral responses to stressful stimuli, and preclinical studies indicate that amygdalar endocannabinoid (eCB) signaling regulates emotional states. This study measured eCB contents in the basolateral (BLA) and central (CeA) amygdala of male and female rats exposed to predator odor stress (bobcat urine) and tested for contextual avoidance 24 h later. Stressed females had lower levels of 2-arachidonoyl glycerol (2-AG) in the BLA and higher levels of anandamide (AEA) in the CeA, while exposure to bobcat urine did not affect amygdalar eCB contents in males. We previously reported that female rats exposed to bobcat urine exhibit blunted acoustic startle reactivity (ASR) 48 h after predator odor stress. Therefore, we tested the hypothesis that intra-BLA injection of a diacylglycerol lipase (DAGL) inhibitor (which would be expected to reduce 2-AG levels in BLA) and intra-CeA injection of a fatty acid amide hydrolase (FAAH) inhibitor (which would be expected to increase AEA levels in CeA) would mimic previously observed predator odor stress-induced reductions in ASR. Contrary to our hypothesis, microinjections of either the DAGL inhibitor DO34 into the BLA or the FAAH inhibitor URB597 into the CeA significantly increased ASR in females compared to vehicle-treated rats. These findings describe sex-specific effects of predator odor stress on amygdalar eCBs, and new roles for amygdalar eCBs in regulating behavior in females.

Stressful events during gestation can have sex-specific effects on brain and behaviour, and may contribute to some of the differences observed in adult stress responding and psychopathology. We investigated the impact of a novel repeated prenatal psychological stress (prenatal predator exposure – PPS) during the last week of gestation in rats on offspring behaviours related to social interaction (play behaviour), open field test (OFT), forced swim test (FST) and sucrose preference test (SP) during the juvenile period and in adulthood. We further examined the role of postnatal environmental, using an enhanced housing condition (EHC), to prevent/rescue any changes. Some effects on anxiety, anhedonia, and stress-related coping behaviours (e.g., OFT, SP and OFT) did not emerge until adulthood. PPS increased OFT anxiety behaviours in adult males, and some OFT and SP behaviours in adult females. Contrary to this, EHC had few independent effects; most were apparent only when combined with PPS. In keeping with age-group differences, juvenile behaviours did not necessarily predict the same adult behaviours although juvenile OFT rearing and freezing, and juvenile FST immobility did predict adult FST immobility and sucrose preference, suggesting that some aspects of depressive behaviours may emerge early and predict adult vulnerability or coping behaviours. Together, these results suggest an important, though complex, role for early life psychological stressors and early life behaviours in creating an adult vulnerability to anxiety or depressive disorders and that environmental factors further modulate the effects of the prenatal stressors.