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Alpha1- and Beta-norepinephrinergic receptors of dorsomedial and ventromedial hypothalamic nuclei modulate panic attack-like defensive behaviour elicited by diencephalic GABAergic neurotransmission disinhibition
Pharmacology Biochemistry and Behavior ( IF 3.6 ) Pub Date : 2024-01-21 , DOI: 10.1016/j.pbb.2024.173710
Andrés Uribe-Mariño , Luiz Luciano Falconi-Sobrinho , Maria Angélica Castiblanco-Urbina , Glauce Regina Pigatto , Farhad Ullah , Juliana Almeida da Silva , Norberto Cysne Coimbra

Gamma-aminobutyric acid (GABA) disinhibition in medial hypothalamus (MH) nuclei of rats elicits some defensive reactions that are considered panic attack-like behaviours. Recent evidence showed that the norepinephrine-mediated system modulates fear-related defensive behaviours organised by MH neurons at least in part via noradrenergic receptors recruitment on midbrain tegmentum. However, it is unknown whether noradrenergic receptors of the MH also modulate the panic attack-like reactions. The aim of this work was to investigate the distribution of noradrenergic receptors in MH, and the effects of either α1-, α2- or β-noradrenergic receptors blockade in the MH on defensive behaviours elaborated by hypothalamic nuclei. Defensive behaviours were evaluated after the microinjection of the selective GABAA receptor antagonist bicuculline into the MH that was preceded by microinjection of either WB4101, RX821002, propranolol (α1-, α2- and β-noradrenergic receptor selective antagonists, respectively), or physiological saline into the MH of male Wistar rats. The α1-, α2- and β-noradrenergic receptors were found in neuronal perikarya of all MH nuclei, and the α2-noradrenergic receptor were also found on glial cells mainly situated in the ventrolateral division of the ventromedial hypothalamic nucleus. The α1- and β-noradrenergic receptors blockade in the MH decreased defensive attention and escape reactions elicited by the intra-MH microinjections of bicuculline. These findings suggest that, despite the profuse distributions of α1-, α2- and β-noradrenergic receptors in the MH, both α1- and β-noradrenergic receptor- rather than α2-noradrenergic receptor-signalling in MH are critical for the neuromodulation of panic-like behaviour.



中文翻译:

下丘脑背内侧和腹内侧核的α1-和β-去甲肾上腺素能受体调节间脑GABA能神经传递去抑制引起的惊恐发作样防御行为

大鼠下丘脑内侧(MH)核中的γ-氨基丁酸(GABA)去抑制会引起一些防御反应,这些反应被认为是惊恐发作样行为。最近的证据表明,去甲肾上腺素介导的系统至少部分通过中脑被盖上去甲肾上腺素能受体的募集来调节 MH神经元组织的与恐惧相关的防御行为。然而,尚不清楚 MH 的去甲肾上腺素能受体是否也调节惊恐发作样反应。这项工作的目的是研究 MH 中去甲肾上腺素能受体的分布,以及 MH 中 α 1 -、α 2 - 或 β-去甲肾上腺素能受体阻断对下丘脑核团防御行为的影响。将选择性 GABA A受体拮抗剂荷包牡丹碱显微注射到 MH 中,然后显微注射WB4101 、RX821002、普萘洛尔(分别为 α 1 -、α 2 - 和 β - 去甲肾上腺素受体选择性拮抗剂),或将生理盐水注入雄性Wistar大鼠的MH中。α 1 -、α 2 - 和β - 去甲肾上腺素能受体存在于所有MH 核的神经元周核中,并且α 2 -去甲肾上腺素能受体也存在于主要位于下丘脑腹内侧核腹外侧区的神经胶质细胞上。MH 中的 α 1 - 和 β - 去甲肾上腺素能受体阻断降低了由 MH 内显微注射荷包牡丹碱引起的防御注意力和逃避反应。这些发现表明,尽管MH 中α 1 -、α 2 - 和 β - 去甲肾上腺素能受体广泛分布,但 MH 中 α 1 - 和 β - 去甲肾上腺素能受体而不是 α 2 - 去甲肾上腺素受体信号传导对于 MH 至关重要。恐慌样行为的神经调节。

更新日期:2024-01-21
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