Vecchiarelli Haley A, Morena Maria, Lee Tiffany T Y, Nastase Andrei S, Aukema Robert J, Leitl Kira D, Gray J Megan, Petrie Gavin N, Tellez-Monnery Kristin J, Hill Matthew N
Neuroscience Graduate Program, University of Calgary, Calgary, AB, T2N 4N1, Canada.
Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.
Neurobiol Stress. 2022 Jul 30;20:100470. doi: 10.1016/j.ynstr.2022.100470. eCollection 2022 Sep.
Research over the past few decades has established a role for the endocannabinoid system in contributing to the neural and endocrine responses to stress exposure. The two endocannabinoid ligands, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), both play roles in regulating the stress response and both exhibit dynamic changes in response to stress exposure. Most of this previous research, however, was conducted in male rodents. Given that, especially in rodents, the stress response is influenced by sex, an understanding of how these dynamic responses of endocannabinoids in response to stress is influenced by sex could provide insight into sex differences of the acute stress response. We exposed adult, Sprague Dawley rats to different commonly utilized acute stress modalities, specifically restraint, swim and foot shock stress. Thirty minutes following stress onset, we excised the amygdala, hippocampus and medial prefrontal cortex, corticolimbic brain regions involved in the stress response, to measure endocannabinoid levels. When AEA levels were altered in response to restraint and swim stress, they were reduced, whereas exposure to foot shock stress led to an increase in the amygdala. 2-AG levels, when they were altered by stress exposure were only increased, specifically in males in the amygdala following swim stress, and in the hippocampus and medial prefrontal cortex overall following foot shock stress. This increase in 2-AG levels following stress only in males was the only sex difference found in stress-induced changes in endocannabinoid levels. There were no consistent sex differences observed. Collectively, these data contribute to our further understanding of the interactions between stress and endocannabinoid function.
过去几十年的研究已确定内源性大麻素系统在促成对压力暴露的神经和内分泌反应中发挥作用。两种内源性大麻素配体，花生四烯乙醇胺（AEA）和2-花生四烯酸甘油酯（2-AG），都在调节应激反应中发挥作用，并且在对压力暴露的反应中都表现出动态变化。然而，此前的大多数研究是在雄性啮齿动物中进行的。鉴于尤其是在啮齿动物中，应激反应受性别影响，了解内源性大麻素对压力的这些动态反应如何受性别影响，可能有助于深入了解急性应激反应的性别差异。我们将成年Sprague Dawley大鼠暴露于不同的常用急性应激模式下，具体为束缚、游泳和足部电击应激。应激开始30分钟后，我们切除杏仁核、海马体和内侧前额叶皮质，这些是参与应激反应的皮质边缘脑区，以测量内源性大麻素水平。当AEA水平因束缚和游泳应激而改变时，它们会降低，而暴露于足部电击应激会导致杏仁核中AEA水平升高。2-AG水平在受到应激暴露影响时仅会升高，具体表现为游泳应激后雄性大鼠杏仁核中的2-AG水平升高，以及足部电击应激后整体海马体和内侧前额叶皮质中的2-AG水平升高。应激后仅雄性大鼠中2-AG水平的这种升高是在应激诱导的内源性大麻素水平变化中发现的唯一性别差异。未观察到一致的性别差异。总体而言，这些数据有助于我们进一步理解应激与内源性大麻素功能之间的相互作用。
