Albrechet-Souza Lucas, Nastase Andrei S, Hill Matthew N, Gilpin Nicholas W
Department of Physiology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
Alcohol & Drug Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
Neurobiol Stress. 2021 Sep 3;15:100387. doi: 10.1016/j.ynstr.2021.100387. eCollection 2021 Nov.
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.
了解应激行为和分子效应中的性别差异对于理解与应激反应回路相关的慢性精神疾病易感性具有重要意义。杏仁核对于情绪学习和产生对应激刺激的行为反应至关重要，临床前研究表明杏仁核内源性大麻素（eCB）信号调节情绪状态。本研究测量了暴露于捕食者气味应激（山猫尿液）的雄性和雌性大鼠基底外侧杏仁核（BLA）和中央杏仁核（CeA）中的eCB含量，并在24小时后测试情境回避情况。应激雌性大鼠BLA中的2-花生四烯酸甘油酯（2-AG）水平较低，CeA中的花生四烯酸乙醇胺（AEA）水平较高，而暴露于山猫尿液对雄性大鼠杏仁核eCB含量没有影响。我们之前报道过，暴露于山猫尿液的雌性大鼠在捕食者气味应激48小时后表现出听觉惊吓反应（ASR）减弱。因此，我们测试了以下假设：向BLA内注射二酰基甘油脂肪酶（DAGL）抑制剂（预期会降低BLA中的2-AG水平）和向CeA内注射脂肪酸酰胺水解酶（FAAH）抑制剂（预期会增加CeA中的AEA水平）会模拟之前观察到的捕食者气味应激诱导的ASR降低。与我们的假设相反，与注射赋形剂的大鼠相比，向BLA内微量注射DAGL抑制剂DO34或向CeA内微量注射FAAH抑制剂URB597均可显著增加雌性大鼠的ASR。这些发现描述了捕食者气味应激对杏仁核eCB的性别特异性影响，以及杏仁核eCB在调节雌性动物行为中的新作用。
