Glucocorticoid-endocannabinoid uncoupling mediates fear suppression deficits after early - Life stress

摘要: Early-life stress (ELS) creates life-long vulnerability to stress-related anxiety disorders through altering and fear systems in the brain. The endocannabinoid system has emerged as an important regulator of response a crosstalk with glucocorticoid system, yet whether it plays role persistent effects ELS remains unanswered. By combining, behavioral, pharmacological biochemical approaches adult male rats, we examined impact on regulation function by glucocorticoids. We employed postnatal limited-nesting/bedding induced between days 2-9 rats. Exposure compromised ability both acute administration mobilize ligand 2-arachidonoyl glycerol (2-AG) hippocampus These findings suggest that compromises coupling hippocampus. Since 2-AG signaling is essential mediating glucocorticoid-induced suppression recall, further glucocorticoids suppress memory recall. While did not affect normative impaired dampen Notably, bypassing directly amplifying hippocampal monoacyl lipase inhibitor produced recall animals exposed ELS. results uncoupling glucocorticoid-endocannabinoid hippocampus, which, turn, relates alterations data provide compelling evidence ELS-induced deficits following could predispose susceptibility psychopathology.