Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Cracow, Poland.
J Physiol Pharmacol. 2019 Oct;70(5). doi: 10.26402/jpp.2019.5.06. Epub 2019 Dec 26.
The endocannabinoid (eCB) system plays a role in the pathophysiology of depression. The aim of this study was to investigate the expression of the eCB synthesizing enzymes (N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) and diacylglycerol lipase α (DAGLα)) and eCB degrading enzymes (fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL)) after acute or chronic administration of antidepressant drugs (imipramine (IMI, 15 mg/kg), escitalopram (ESC, 10 mg/kg) and tianeptine (TIA, 10 mg/kg)). eCB metabolizing enzymes were altered in drug-dependent and brain region-specific fashion. After IMI treatment a reduction was noted in the expression of FAAH protein in the dorsal striatum, MAGL in the frontal cortex and DAGLα in the cerebellum. On the other hand, ESC treatment provoked an increase in the MAGL expression in the prefrontal cortex or NAPE-PLD and in DAGLα in the hippocampus and dorsal striatum, while reducing the FAAH expression in the dorsal striatum. TIA administration increased the levels of all enzymes in the prefrontal cortex as well as elevated DAGLα expression in the frontal cortex and dorsal striatum. In conclusion, our results indicate that changes in the eCBs levels after antidepressant drug treatment were related to the expression of their metabolizing enzymes.
内源性大麻素（eCB）系统在抑郁症的病理生理学中起作用。本研究旨在探讨急性或慢性给予抗抑郁药（丙咪嗪（IMI，15mg/kg）、艾司西酞普兰（ESC，10mg/kg）和噻奈普汀（TIA，10mg/kg）后，eCB 合成酶（N-酰基磷脂酰乙醇胺磷脂酶 D（NAPE-PLD）和二酰基甘油脂肪酶α（DAGLα））和 eCB 降解酶（脂肪酸酰胺水解酶（FAAH）和单酰基甘油脂肪酶（MAGL）的表达。eCB 代谢酶以药物依赖和脑区特异性的方式发生改变。在 IMI 治疗后，背侧纹状体中的 FAAH 蛋白表达减少，额皮质中的 MAGL 表达减少，小脑中的 DAGLα 表达减少。另一方面，ESC 治疗导致前额叶皮质中的 MAGL 表达增加，海马和背侧纹状体中的 NAPE-PLD 和 DAGLα 表达增加，而背侧纹状体中的 FAAH 表达减少。TIA 给药增加了前额叶皮质中所有酶的水平，并增加了额皮质和背侧纹状体中的 DAGLα 表达。总之，我们的结果表明，抗抑郁药治疗后 eCB 水平的变化与它们代谢酶的表达有关。
