Role of endocannabinoid neurotransmission in the insular cortex on cardiovascular, autonomic and behavioral responses evoked by acute restraint stress in rats

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2025-03-04 DOI:10.1016/j.neuropharm.2025.110404

Ivaldo J.A. Belem-Filho , Ana C.V. Godoy , Cristiane Busnardo , Alana T. Frias , Helio Zangrossi Jr. , Bruno Del Bianco Borges , Ana C.F. Herval , Fernando M.A. Correa , Carlos C. Crestani , Fernando H.F. Alves

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引用次数: 0

Abstract

This study aimed to investigate the role of endocannabinoid mechanisms present within the insular cortex (IC) on cardiovascular, autonomic and anxiogenic-like responses evoked by an acute session of restraint in rats. For this, bilateral guide cannulas directed to the IC were implanted in male Wistar rats for intrabrain microinjection of the selective CB₁ receptor antagonist AM251, the selective TRPV1 receptor antagonist capsazepine, the fatty acid amide hydrolase (FAAH) inhibitor URB597 or the monoacylglycerol lipase (MAGL) inhibitor JZL184. The effects of pharmacological treatments were evaluated on restraint-evoked increases in blood pressure and heart rate, sympathetically-mediated cutaneous vasoconstriction and in delayed anxiogenic-like effect assessed 24h after stress exposure in the elevated plus maze (EPM) and open field (OF). We observed that acute restraint stress decreased the exploration of both EPM open arms and OF center region in animals treated with vehicle into the IC, thus indicating an anxiogenic-like effect. Inhibition of MAGL within the IC evoked by local treatment with JZL184 avoided the restraint-evoked anxiogenic effect. IC treatment with JZL184 also attenuated the tachycardia during restraint. The other pharmacological treatments did not modify the cardiovascular, autonomic and behavioral responses evoked by restraint. Taken together, these findings suggest that endocannabinoid neurotransmission in the IC, potentially acting through the endocannabinoid 2-arachidonoylglycerol, plays an inhibitory role in both tachycardia and anxiogenic-like effect evoked by stressful events.

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脑岛皮质内源性大麻素神经传递对大鼠急性约束应激引起的心血管、自主神经和行为反应的作用

本研究旨在探讨岛叶皮质（IC）内源性大麻素在大鼠急性约束引起的心血管、自主神经和焦虑样反应中的作用。为此，在雄性Wistar大鼠中植入双侧引导管，在脑内微量注射选择性CB1受体拮抗剂AM251、选择性TRPV1受体拮抗剂capsazepine、脂肪酸酰胺水解酶（FAAH）抑制剂URB597或单酰基甘油脂肪酶（MAGL）抑制剂JZL184。在升高迷宫（EPM）和开阔场（of）应激暴露24小时后，评估药物治疗对抑制引起的血压和心率升高、交感介导的皮肤血管收缩和延迟焦虑样效应的影响。我们观察到，急性约束应激减少了动物对EPM张开臂和of中心区域的探索，从而表明了一种类似焦虑的作用。局部用JZL184抑制IC内的MAGL，避免了抑制引起的焦虑效应。用JZL184进行IC治疗也能减轻抑制期间的心动过速。其他药物治疗并没有改变约束引起的心血管、自主神经和行为反应。综上所述，这些发现表明内源性大麻素在IC中的神经传递，可能通过内源性大麻素2-花生四烯醇甘油起作用，在应激事件引起的心动过速和焦虑样效应中起抑制作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).