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在被蝰蛇威胁的猎物的下丘脑中阻断κ-阿片受体可减少焦虑和惊恐样行为。

Kappa-opioid receptor blockade in the inferior colliculus of prey threatened by pit vipers decreases anxiety and panic-like behaviour.

作者信息

Calvo Fabrício, Dos Anjos-Garcia Tayllon, Paschoalin-Maurin Tatiana, Bazaglia-de-Sousa Guilherme, de Paula Rodrigues Bruno Mangili, Lobão-Soares Bruno, Almada Rafael Carvalho, Wotjak Carsten T, Coimbra Norberto Cysne

机构信息

Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, School of Medicine of Ribeirão Preto of the University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.

Ophidiarium LNN-FMRP-USP/INeC, Ribeirão Preto School of Medicine of the University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.

出版信息

Acta Neuropsychiatr. 2024 Oct 7:1-13. doi: 10.1017/neu.2024.30.

DOI:10.1017/neu.2024.30
PMID:39370934
Abstract

The dorsal midbrain comprises dorsal columns of the periaqueductal grey matter and corpora quadrigemina. These structures are rich in beta-endorphinergic and leu-enkephalinergic neurons and receive GABAergic inputs from substantia nigra pars reticulata. Although the inferior colliculus (IC) is mainly involved in the acoustic pathways, the electrical and chemical stimulation of central and pericentral nuclei of the IC elicits a vigorous defensive behaviour. The defensive immobility and escape elicited by IC activation is commonly related to panic-like emotional states. To investigate the role of κ-opioid receptor of the IC in the antiaversive effects of endogenous opioid receptor blockade in a dangerous situation, male Wistar rats were pretreated in the IC with the κ-opioid receptor-selective antagonist nor-binaltorphimine at different concentrations and submitted to the non-enriched polygonal arena for a snake panic test in the presence of a rattlesnake and, after 24 h, prey were resubmitted to the experimental context. The snakes elicited in prey a set of antipredatory behaviours, such as the anxiety-like responses of defensive attention and risk assessment, and the panic-like reactions of defensive immobility and either escape or active avoidance during the elaboration of unconditioned and conditioned fear-related responses. Pretreatment of the IC with microinjections of nor-binaltorphimine at higher concentrations significantly decreased the frequency and duration of both anxiety- and panic-attack-like behaviours. These findings suggest that κ-opioid receptor blockade in the IC causes anxiolytic- and panicolytic-like responses in threatening conditions, and that kappa-opioid receptor-selective antagonists can be a putative coadjutant treatment for panic syndrome treatment.

摘要

中脑背侧由导水管周围灰质柱和四叠体组成。这些结构富含β-内啡肽能和亮脑啡肽能神经元,并接受来自黑质网状部的GABA能输入。虽然下丘主要参与听觉通路,但对下丘中央核和中央周围核的电刺激和化学刺激会引发强烈的防御行为。下丘激活引发的防御性不动和逃避通常与恐慌样情绪状态有关。为了研究下丘κ-阿片受体在内源性阿片受体阻断在危险情况下的抗厌恶作用中的作用,将雄性Wistar大鼠在不同浓度的κ-阿片受体选择性拮抗剂去甲纳曲酮预处理下丘后,置于非丰富的多边形场地中进行响尾蛇恐慌试验,在有响尾蛇的情况下,24小时后,将猎物重新置于实验环境中。响尾蛇在猎物中引发了一系列反捕食行为,如防御性注意和风险评估的焦虑样反应,以及在形成无条件和条件性恐惧相关反应过程中防御性不动和逃避或主动回避的恐慌样反应。用较高浓度的去甲纳曲酮微量注射预处理下丘显著降低了焦虑样和恐慌样行为的频率和持续时间。这些发现表明,下丘中的κ-阿片受体阻断在威胁条件下会引起抗焦虑和抗恐慌样反应,并且κ-阿片受体选择性拮抗剂可能是恐慌综合征治疗的一种假定辅助治疗方法。

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