RATIONALE The functional role of the endocannabinoid system (ECS) and Transient Receptor Potential Vanilloid type-1 (TRPV1) within the Nucleus Accumbens shell (NAc shell) remains unknown. Preclinical studies in rodents have reported that the ECS modulates emotional responses such as anxiety. The NAc shell has a high density of synaptically co-localized cannabinoid receptor type-1 (CB1R) and TRPV1, suggesting a potential involvement in the modulation of anxiety. OBJECTIVES The present study aims to establish the role of ECS-TRPV1 interactions within the NAc shell and its effects on anxiety. It is hypothesized that the neurochemical regulation elicited by ECS within the NAc shell mediates anxiety-like behaviors in rodents. METHODS In this study, male Sprague Dawley rats were implanted with bilateral brain cannula targeting the NAc shell. Following recovery from surgery, animals received microinfusion pretreatments (0, 0.125, 0.5 nmol/0.4 µl) of N-arachidonoyl-serotonin (AA-5-HT), a dual blocker of the endocannabinoid-inactivating enzyme, fatty acid amide hydrolase (FAAH) and a TRPV1 antagonist in the NAc shell. Following treatment, animals were tested in an elevated plus maze (EPM) paradigm for a period of 5 minutes. At the end of the experiment, animals were sacrificed and their brains collected for histological and biochemical analysis. RESULTS Results showed that animals treated with AA-5-HT in a dose dependent manner spent significantly more time in the open arms than vehicle-treated animals. In addition, AA-5-HT administration induced a significant downregulation of CB1R expression in the NAc shell. CONCLUSIONS The present findings suggest that the ECS within the NAc shell modulates anxiety-like behaviors via FAAH and CB1R activity.

中文翻译：

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伏伏核壳内对vanvanilloid受体TRPV1和内源性大麻素酶FAAH的阻断引发雄性大鼠的抗焦虑作用。

原理内伏核壳（NAc壳）内的内源性大麻素系统（ECS）和瞬态潜在潜在香草味1型（TRPV1）的功能作用尚不清楚。啮齿动物的临床前研究报告称，ECS调节情绪反应，如焦虑症。NAc外壳具有高密度的突触共定位1型大麻素受体（CB1R）和TRPV1，表明可能参与了焦虑的调节。目的本研究旨在建立ECS-TRPV1相互作用在NAc壳内的作用及其对焦虑的影响。据推测，ECS在NAc壳内引起的神经化学调节介导了啮齿动物的焦虑样行为。方法在本研究中，雄性Sprague Dawley大鼠植入了靶向NAc壳的双侧脑套管。从手术中恢复后，动物接受了微注射预处理（0，0.125，0.5 nmol / 0.4 µl）N-花生四烯酸-血清素（AA-5-HT），一种内源性大麻素失活酶，脂肪酸酰胺水解酶（FAAH）的双重阻断剂）和NAc外壳中的TRPV1拮抗剂。治疗后，在高架迷宫（EPM）模式下对动物进行5分钟的测试。实验结束时，处死动物并收集大脑进行组织学和生化分析。结果结果表明，以AA5-HT剂量依赖性方式治疗的动物在张开双臂上所花费的时间比用媒介物处理的动物要多得多。此外，AA-5-HT的使用引起了NAc壳中CB1R表达的显着下调。