Steiner Michel A, Wotjak Carsten T
Max Planck Institute of Psychiatry, Neuroplasticity Group, Kraepelinstrasse, Munich, Germany.
Prog Brain Res. 2008;170:397-432. doi: 10.1016/S0079-6123(08)00433-0.
The endocannabinoid system has been recognized as a major neuromodulatory system, which functions to maintain brain homoeostasis. Endocannabinoids are synthesized and released from the postsynapse and act as retrograde neuronal messengers, which bind to cannabinoid type 1 receptors at the presynapse. Here, they inhibit the release of neurotransmitters, including glutamate and GABA. By these means, endocannabinoids control the activation of various neuronal circuits including those involved in neuroendocrine stress processing. Accordingly, exogenous cannabinoids such as the major active component of marijuana, Delta(9)-tetrahydrocannabinol, have long been known to activate the major neuroendocrine stress response system of mammals, the hypothalamic-pituitary-adrenocortical (HPA) axis. However, the function of the endocannabinoid system in the regulation of stress hormone secretion has only recently begun to be understood. It is the focus of the present review to provide the reader with an overview of our current knowledge of the role of endocannabinoid signalling in HPA axis regulation under basal as well as under stressful conditions. This includes the specific sites of action, potential underlying neuronal pathways and interactions between behavioural and neuroendocrine stress coping. Furthermore, the potential role of HPA axis activity dysregulations, caused by deficits in the endocannabinoid system, for the pathophysiology of psychiatric diseases is discussed.
内源性大麻素系统已被公认为一种主要的神经调节系统，其功能是维持大脑的内环境稳定。内源性大麻素在突触后合成并释放，作为逆行神经元信使，与突触前的1型大麻素受体结合。在这里，它们抑制包括谷氨酸和γ-氨基丁酸在内的神经递质的释放。通过这些方式，内源性大麻素控制各种神经元回路的激活，包括那些参与神经内分泌应激处理的回路。因此，长期以来人们都知道，外源性大麻素，如大麻的主要活性成分Δ⁹-四氢大麻酚，会激活哺乳动物主要的神经内分泌应激反应系统——下丘脑-垂体-肾上腺皮质（HPA）轴。然而，内源性大麻素系统在调节应激激素分泌中的作用直到最近才开始被了解。本综述的重点是向读者概述我们目前对基础状态以及应激状态下内源性大麻素信号在HPA轴调节中的作用的认识。这包括作用的特定部位、潜在的神经元通路以及行为和神经内分泌应激应对之间的相互作用。此外，还讨论了内源性大麻素系统缺陷导致的HPA轴活动失调在精神疾病病理生理学中的潜在作用。
