Histaminergic transmission potentiates post-traumatic stress-induced expression of anxiety in mice

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2025-06-21 DOI:10.1016/j.neuropharm.2025.110564

Vaibhav Maturkar, Richa Patel, Chhatrapal Patel, Venu Anand Das Vaishnav, Nishant Sudhir Jain

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Abstract

Post-traumatic stress is associated with an increased expression of anxiety traits and is reported to be accompanied by altered brain histamine content. However, the contribution of the central histaminergic system in the stress induced anxiety, still remains unclear. Therefore, the present study explored the plausible role of central histaminergic transmission in stress-induced anxiety measures in mice using LDB test and in the expression of CORT, CREB, or BDNF levels in the whole brain, PFC, amygdala, and hippocampus of mice. The mice were exposed to the SPS protocol and subsequently left undisturbed for 7 days. On the 8th day, non-SPS/SPS exposed mice were treated i.c.v with histaminergic agents such as histamine, or histamine precursor, l-histidine, H₁ agonist, FMPH, H₂ agonist, amthamine, H₁ antagonist, cetirizine or H₂ antagonist, ranitidine or H₃ inverse agonist, thioperamide and thereafter evaluated for changes in expression of anxiety followed by estimation of CORT, CREB and BDNF levels in brain. Results revealed that SPS-exposed mice elicit heightened anxiety-like behavior accompanied by increased levels of blood or brain histamine and CORT with reduced BDNF/CREB expression in the all-brain tissues. Administration of histaminergic enhancing agents to SPS-exposed mice potentiated the higher expression of anxiety, also further enhanced CORT, and diminished the BDNF/CREB expression in all brain regions. Conversely, central injection of the H₁ receptor antagonist, cetirizine (0.1 μg/mouse) or H₂ receptor antagonist, ranitidine (10 μg/mouse, i.c.v) to SPS mice completely alleviated all the stressed induced changes while H₃ receptor inverse agonist, thioperamide (2, 10 μg/mouse) failed to affect CORT but restored basal anxiety, CREB and BDNF expression. Thus, the blockade of central histamine H₁/H₂/H₃ receptors might mitigate SPS-induced anxiety-like manifestations by extenuating the SPS-induced CORT, CREB, and BDNF expression.

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组胺能传递增强小鼠创伤后应激诱导的焦虑表达。

创伤后应激与焦虑特征的表达增加有关，据报道还伴有脑组胺含量的改变。然而，中枢组胺能系统在应激性焦虑中的作用仍不清楚。因此，本研究通过LDB测试探讨了中枢组胺能传递在小鼠应激性焦虑测量中的可能作用，以及在小鼠全脑、PFC、杏仁核和海马中CORT、CREB或BDNF水平表达中的可能作用。小鼠暴露于SPS方案，随后不受干扰7天。在第8天，非SPS/SPS暴露小鼠用组胺能药物如组胺或组胺前体、l-组氨酸、H1激动剂、FMPH、H2激动剂、氨胺、H1拮抗剂、西替利嗪或H2拮抗剂、雷尼替丁或H3逆激动剂、硫哌丁等进行静脉注射，随后评估焦虑表达的变化，并评估脑内CORT、CREB和BDNF水平。结果显示，暴露于sps的小鼠会引起焦虑样行为的增加，同时血液或脑组胺和CORT水平升高，全脑组织中BDNF/CREB表达降低。给暴露于sps的小鼠注射组胺能增强剂，增强了焦虑的高表达，也进一步提高了CORT，并降低了所有脑区BDNF/CREB的表达。相反，中枢注射H1受体拮抗剂西替利嗪（0.1 μg/只）或H2受体拮抗剂雷尼替丁（10 μg/只，i.c.v）完全缓解了应激引起的所有变化，而H3受体逆激动剂硫哌丁胺（2,10 μg/只）对CORT没有影响，但恢复了基础焦虑、CREB和BDNF的表达。因此，阻断中枢组胺H1/H2/H3受体可能通过减轻sps诱导的CORT、CREB和BDNF的表达来减轻sps诱导的焦虑样表现。

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).