Department of Internal Medicine, Jagiellonian University Medical College, Skawińska 8, PL 31-066 Kraków, Poland; Department of Toxicology, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, PL 30-688 Kraków, Poland.
Institute of Pharmacology, Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Smętna 12, PL 31-343 Kraków, Poland.
Neurotoxicology. 2017 Dec;63:13-20. doi: 10.1016/j.neuro.2017.08.012. Epub 2017 Sep 1.
The endocannabinoid (eCB) system plays a significant role in the pathophysiology of depression. The potential participation of this system in the mechanism of action of antidepressants has been highlighted in recent years. The aim of this study was to investigate the expression of cannabinoid (CB) receptors using Western blot and CB receptor density using autoradiography after acute or chronic administration of antidepressant drugs [imipramine (IMI, 15mg/kg), escitalopram (ESC, 10mg/kg) and tianeptine (TIA, 10mg/kg)]. Antidepressants given chronically elevated CB receptor density in the cortical structures and hippocampal areas, while a decrease of CB receptor density was observed in the striatum after IMI and ESC treatment. The CB receptor expression decreases in the dorsal striatum after chronic administration of IMI and ESC or the receptor rise in the hippocampus after chronic ESC and TIA treatment were confirmed using Western blot analyses. An increase in the CB receptor expression was observed in the cortical structures and hippocampus after chronic administration of ESC and TIA, while a decrease in this expression was noted in the striatum and cerebellum after chronic IMI treatment. Our results provide clear evidence that the antidepressant exposures provoke some modulations within the eCB system through CB receptors.
内源性大麻素（eCB）系统在抑郁症的病理生理学中起着重要作用。近年来，人们强调了该系统在抗抑郁药作用机制中的潜在参与。本研究旨在通过Western blot 研究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）]后大麻素（CB）受体的表达，并通过放射自显影研究 CB 受体密度。慢性给予抗抑郁药可升高皮质结构和海马区的 CB 受体密度，而 IMI 和 ESC 处理后纹状体的 CB 受体密度降低。Western blot 分析证实，慢性给予 IMI 和 ESC 后背侧纹状体的 CB 受体表达下降，而慢性 ESC 和 TIA 处理后海马的受体上升。慢性给予 ESC 和 TIA 后皮质结构和海马的 CB 受体表达增加，而慢性 IMI 处理后纹状体和小脑的 CB 受体表达下降。我们的研究结果提供了明确的证据，表明抗抑郁药暴露会通过 CB 受体引起 eCB 系统的一些调节。
