Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea.
Neuropharmacology. 2012 Feb;62(2):1034-43. doi: 10.1016/j.neuropharm.2011.10.013. Epub 2011 Nov 4.
The transient receptor potential vanilloid type 1 channel (TRPV1) receptors are expressed in various regions of the brain. Much less is known about whether TRPV1 receptors affect higher brain functions. In the present study, we demonstrated that TRPV1-knockout (TRPV1KO) mice showed antidepressant-like behaviors in a novelty-suppressed feeding test and forced swim test when compared to wild-type (WT) mice. Additionally, TRPV1KO mice exhibited increased aggressiveness and reduced social interactions in a social dominance test and social interaction test. TRPV1KO mice showed reduced short-term memory and normal long-term memory in a novel object recognition test and passive avoidance test versus WT mice. Based on these behavioral data, we investigated changes in specific receptors related to depression, anxiety, and memory in the brains of TRPV1KO and WT mice. Binding of [(3)H]-8-OH-DPAT was significantly higher in the frontal associated cortex (FrA), nucleus accumbens (NAc), and the cingulate cortex (CC) of TRPV1KO mice than WT mice, while the expression of 5-HT(1A) receptors was higher in the FrA, NAc, and cortex of TRPV1KO mice than WT mice. [(3)H]-flunitrazepam binding was also significantly higher in the FrA, striatum (CPU), and the CC of TRPV1KO versus WT mice. In contrast, [(3)H]-musicmol binding in the FrA, CPU, NAc, CC, and the dentate gyrus (DG) was significantly lower in TRPV1KO mice than WT mice. The expression of GABA(A)γ(2) was higher in the NAc, CPU, and cortex of TRPV1KO versus WT mice, whereas the expression of GABA(A)α(2) was lower in the FrA, CPU, NAc, and cortex in TRPV1KO mice than WT mice. Finally, [(3)H]-MK-801 binding was decreased in the CPU and CA1 of TRPV1KO versus WT mice. The expression of NR2A was lower in the hippocampus of TRPV1KO versus WT mice. These data suggest that the loss of TRPV1 results in antidepressant-like, anxiolytic, abnormal social and reduced memorial behaviors due to changes in expression of 5-HT(1A), GABA(A,) and NMDA receptors. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
瞬时受体电位香草酸型 1 通道（TRPV1）受体存在于大脑的各个区域。目前还不太清楚 TRPV1 受体是否会影响大脑的高级功能。在本研究中，与野生型（WT）小鼠相比，TRPV1 敲除（TRPV1KO）小鼠在新颖性抑制进食试验和强迫游泳试验中表现出抗抑郁样行为。此外，TRPV1KO 小鼠在社会优势试验和社会互动试验中表现出攻击性增强和社交互动减少。与 WT 小鼠相比，TRPV1KO 小鼠在新物体识别试验和被动回避试验中表现出短期记忆减少和正常的长期记忆。基于这些行为数据，我们研究了 TRPV1KO 和 WT 小鼠大脑中与抑郁、焦虑和记忆相关的特定受体的变化。与 WT 小鼠相比，TRPV1KO 小鼠的额前联合皮层（FrA）、伏隔核（NAc）和扣带皮层（CC）中[（3）H]-8-OH-DPAT 的结合显著增加，而 FrA、NAc 和 TRPV1KO 小鼠的皮层中 5-HT（1A）受体的表达也高于 WT 小鼠。[（3）H]-氟硝西泮结合也显著高于 FrA、纹状体（CPU）和 CC 的 TRPV1KO 与 WT 小鼠。相比之下，TRPV1KO 小鼠的 FrA、CPU、NAc、CC 和齿状回（DG）中的[（3）H]-音乐摩尔结合显著低于 WT 小鼠。TRPV1KO 小鼠的 NAc、CPU 和皮层中 GABA（A）γ（2）的表达高于 WT 小鼠，而 FrA、CPU、NAc 和皮层中的 GABA（A）α（2）的表达则低于 WT 小鼠。最后，[（3）H]-MK-801 结合在 TRPV1KO 与 WT 小鼠的 CPU 和 CA1 中减少。TRPV1KO 小鼠的海马中 NR2A 的表达较低。这些数据表明，由于 5-HT（1A）、GABA（A）和 NMDA 受体表达的变化，TRPV1 的缺失导致抗抑郁样、抗焦虑、异常的社交和记忆减少行为。本文是特刊“创伤后应激障碍”的一部分。
