关键词: 2-AG, 2-arachidonoyl glycerol AEA, anandamide CB1, cannabinoid type 1 receptor CRH, corticotropin releasing hormone CRH-R1, CRH receptor type 1 Corticolimbic Endocannabinoid FAAH, fatty acid amide hydrolase HPA, hypothalamic-pituitary-adrenal Rats SEM, standard error of the mean Sex differences Stress Stressor modality THC, delta-9-tetrahydrocannabinol 2-AG, 2-arachidonoyl glycerol AEA, anandamide CB1, cannabinoid type 1 receptor CRH, corticotropin releasing hormone CRH-R1, CRH receptor type 1 Corticolimbic Endocannabinoid FAAH, fatty acid amide hydrolase HPA, hypothalamic-pituitary-adrenal Rats SEM, standard error of the mean Sex differences Stress Stressor modality THC, delta-9-tetrahydrocannabinol

来  源:   DOI:10.1016/j.ynstr.2022.100470   PDF(Pubmed)

Abstract:
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.
摘要:
过去几十年的研究已经确立了内源性大麻素系统在促进应激暴露的神经和内分泌反应中的作用。两种内源性大麻素配体,anandamide(AEA)和2-花生四酰基甘油(2-AG),两者都在调节应激反应中起作用,并且都表现出响应于压力暴露的动态变化。以前的大部分研究,然而,在雄性啮齿动物中进行。鉴于此,尤其是在啮齿动物中,应激反应受性别的影响,了解内源性大麻素对应激反应的这些动态反应是如何受性别影响的,可以深入了解急性应激反应的性别差异。我们暴露了成年人,SpragueDawley大鼠对不同的常用急性应激方式,特别是克制,游泳和脚部电击压力。压力发作后30分钟,我们切除了杏仁核,海马和内侧前额叶皮质,涉及应激反应的皮质边缘大脑区域,测量内源性大麻素水平。当AEA水平因束缚和游泳压力而改变时,他们减少了,而暴露于足部电击压力会导致杏仁核增加。2-AG级别,当它们因压力暴露而改变时,它们只会增加,特别是在游泳压力下杏仁核中的雄性,在足休克后的海马和内侧前额叶皮层中。仅在男性中应激后2-AG水平的增加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。没有观察到一致的性别差异。总的来说,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.
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