Endogenous cannabinoids (endocannabinoids, eCB) are expressed throughout the body and contribute to regulation of the hypothalamo-pituitary-adrenal (HPA) axis and general stress reactivity. This study assessed the contributions of CB1 receptors (CB1R) in the modulation of basal and stress-induced neural and HPA axis activities. Catheterized adult male rats were placed in chambers to acclimate overnight, with their catheters connected and exteriorized from the chambers for relatively stress-free remote injections. The next morning, the CB1R antagonist AM251 (1 or 2 mg/kg) or vehicle was administered, and 30 min later, rats were exposed to loud noise stress (30 min) or no noise (basal condition). Blood, brains, pituitary and adrenal glands were collected immediately after the procedures for analysis of c-fos and CB1R mRNAs, corticosterone (CORT) and adrenocorticotropin hormone (ACTH) plasma levels. Basally, CB1R antagonism induced c-fos mRNA in the basolateral amygdala (BLA) and auditory cortex (AUD) and elevated plasma CORT, indicating disruption of eCB-mediated constitutive inhibition of activity. CB1R blockade also potentiated stress-induced hormone levels and c-fos mRNA in several regions such as the bed nucleus of the stria terminalis (BST), lateral septum (LS), and basolateral amygdala (BLA) and the paraventricular nucleus of the hypothalamus (PVN). CB1R mRNA was detected in all central tissues investigated, and the adrenal cortex, but at very low levels in the anterior pituitary gland. Interestingly, CB1R mRNA was rapidly and bidirectionally regulated in response to stress and/or antagonist treatment in some regions. eCBs therefore modulate the HPA axis by regulating both constitutive and activity-dependent inhibition at multiple levels.

中文翻译：

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远程 CB1 受体拮抗剂给药揭示了强直性和阶段性内源性大麻素神经内分泌调节的多个部位

内源性大麻素（endocannabinoids，eCB）在全身表达，有助于调节下丘脑-垂体-肾上腺（HPA）轴和一般应激反应。本研究评估了 CB1 受体 (CB1R) 在调节基础和压力诱导的神经和 HPA 轴活动中的贡献。插入导管的成年雄性大鼠被放置在腔室中以适应过夜，将它们的导管连接并从腔室外部化，以进行相对无压力的远程注射。第二天早上，给予 CB1R 拮抗剂 AM251（1 或 2 毫克/公斤）或载体，30 分钟后，大鼠暴露于噪音压力（30 分钟）或无噪音（基础条件）。在 c-fos 和 CB1R mRNA 分析程序后立即收集血液、大脑、垂体和肾上腺，皮质酮 (CORT) 和促肾上腺皮质激素 (ACTH) 血浆水平。基本上，CB1R 拮抗作用在基底外侧杏仁核 (BLA) 和听觉皮层 (AUD) 中诱导 c-fos mRNA 和血浆 CORT 升高，表明 eCB 介导的本构抑制活动的破坏。CB1R 阻断还增强了若干区域的应激诱导的激素水平和 c-fos mRNA，例如终纹床核 (BST)、外侧隔 (LS) 和基底外侧杏仁核 (BLA) 和下丘脑室旁核。 PVN）。在所有研究的中枢组织和肾上腺皮质中检测到 CB1R mRNA，但在垂体前叶中的水平非常低。有趣的是，CB1R mRNA 在某些区域被快速双向调节以响应压力和/或拮抗剂治疗。