Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA; School of Basic and Applied Sciences, Dayananda Sagar University, Bangalore, India.
J Psychiatr Res. 2020 Jan;120:103-112. doi: 10.1016/j.jpsychires.2019.10.010. Epub 2019 Oct 11.
Major depressive disorder (MDD) is common, often under-treated and a leading cause of disability and mortality worldwide. The causes of MDD remain unclear, including the role of the endocannabinoid system. Intriguingly, the prevalence of depression is significantly greater in women than men. In this study we examined the role of endocannabinoids in depressive behavior. The levels of endocannabinoids, N-arachidonoyl ethanolamide (AEA) and 2-arachidonoyl glycerol (2-AG) were measured along with brain derived neurotrophic factor (BDNF) in postmortem ventral striata of female patients with MDD and non-psychiatric controls, and in Wistar Kyoto (WKY) rat, a selectively inbred strain of rat widely used for testing the depressive behavior. The effect of pharmacological elevation of endocannabinoids through inhibition of their catabolizing enzymes (fatty acid amide hydrolase [FAAH] and monoacyl glycerol lipase [MAGL]) on depressive-like phenotype was also assessed in WKY rat. The findings showed lower levels of endocannabinoids and BDNF in the ventral striata of MDD patients and WKY rats. A dual inhibitor of FAAH and MAGL, JZL195, elevated the endocannabinoids and BDNF levels in ventral striatum, and reduced the depressive-like phenotype in female WKY rats. Collectively, our study suggests a blunted ventral striatal endocannabinoid and BDNF signaling in depressive behavior and concludes that endocannabinoid enhancing agents may have an antidepressant effect.
重度抑郁症（MDD）很常见，往往治疗不足，是全球残疾和死亡的主要原因。MDD 的病因仍不清楚，包括内源性大麻素系统的作用。有趣的是，抑郁症的患病率在女性中明显高于男性。在这项研究中，我们研究了内源性大麻素在抑郁行为中的作用。我们测量了 MDD 女性患者和非精神病对照患者死后腹侧纹状体中的内源性大麻素、N-花生四烯酸乙醇酰胺（AEA）和 2-花生四烯酸甘油（2-AG）水平，以及内源性大麻素水平，以及广泛用于测试抑郁行为的 Wistar Kyoto（WKY）大鼠。还评估了通过抑制其代谢酶（脂肪酸酰胺水解酶[FAAH]和单酰基甘油脂肪酶[MAGL]）升高内源性大麻素对 WKY 大鼠抑郁样表型的影响。研究结果显示，MDD 患者和 WKY 大鼠腹侧纹状体中的内源性大麻素和 BDNF 水平较低。FAAH 和 MAGL 的双重抑制剂 JZL195 可升高腹侧纹状体中的内源性大麻素和 BDNF 水平，并减少雌性 WKY 大鼠的抑郁样表型。总之，我们的研究表明，在抑郁行为中，腹侧纹状体中的内源性大麻素和 BDNF 信号减弱，并且内源性大麻素增强剂可能具有抗抑郁作用。
