Hill Matthew N, Hillard Cecilia J, Bambico Francis R, Patel Sachin, Gorzalka Boris B, Gobbi Gabriella
Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA.
Trends Pharmacol Sci. 2009 Sep;30(9):484-93. doi: 10.1016/j.tips.2009.06.006. Epub 2009 Sep 3.
The endocannabinoid system is a neuromodulatory system which is known to regulate emotional, cognitive, neurovegetative and motivational processes. Substantial evidence has accumulated implicating a deficit in endocannabinoid in the etiology of depression; accordingly, pharmacological augmentation of endocannabinoid signaling could be a novel target for the pharmacotherapy of depression. Within preclinical models, facilitation of endocannabinoid neurotransmission evokes both antidepressant and anxiolytic effects. Similar to the actions of conventional antidepressants, enhancement of endocannabinoid signaling can enhance serotonergic and noradrenergic transmission; increase cellular plasticity and neurotrophin expression within the hippocampus; and dampen activity within the neuroendocrine stress axis. Furthermore, limbic endocannabinoid activity is increased by both pharmacological and somatic treatments for depression, and, in turn, appears to contribute to some of the neuroadaptive alterations elicited by these treatments. These preclinical findings support the rationale for the clinical development of agents which inhibit the cellular uptake and/or metabolism of endocannabinoids in the treatment of mood disorders.
内源性大麻素系统是一种神经调节系统，已知其可调节情绪、认知、神经植物性和动机过程。大量证据表明，内源性大麻素缺乏与抑郁症的病因有关；因此，增强内源性大麻素信号传导可能是抑郁症药物治疗的一个新靶点。在临床前模型中，促进内源性大麻素神经传递会产生抗抑郁和抗焦虑作用。与传统抗抑郁药的作用类似，增强内源性大麻素信号传导可增强5-羟色胺能和去甲肾上腺素能传递；增加海马体内的细胞可塑性和神经营养因子表达；并抑制神经内分泌应激轴的活性。此外，抑郁症的药物治疗和躯体治疗均可增加边缘系统内源性大麻素的活性，反过来，这似乎有助于这些治疗引起的一些神经适应性改变。这些临床前研究结果支持了开发抑制内源性大麻素细胞摄取和/或代谢的药物用于治疗情绪障碍的临床依据。
