Stimulation of central histaminergic transmission attenuates diazepam-induced motor disturbance on rota-rod and beam walking tests in mice.

IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES Behavioural Pharmacology Pub Date : 2024-09-01 Epub Date: 2024-07-19 DOI:10.1097/FBP.0000000000000786
Richa Patel, Nishant Sudhir Jain
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Abstract

Diazepam administration has been shown to influence the release of histamine in various brain areas involved in motor behavior. Therefore, the present study explored the plausible regulatory role of the central histaminergic system in diazepam-induced deficits in motor performance in mice using the rota-rod and beam walking tests. In this study, several doses of diazepam (0.5, 1, 2, and 3 mg/kg, i.p.) were assessed in mice for changes in motor performance on the rota-rod and beam walking test. In addition, the brain histamine levels were determined after diazepam administration, and the diazepam-induced motor deficits were assessed in mice, pretreated centrally (intracerebroventricular) with histaminergic agents such as histamine (0.1, 10 µg), histamine precursor (L-histidine: 0.1, 2.5 µg), histamine neuronal releaser/H 3 receptor antagonist (thioperamide: 0.5, 10 µg), H 1 and H 2 receptor agonist [2-(3-trifluoromethylphenyl) histamine (FMPH: 0.1, 6.5 µg; amthamine: 0.1, 5 µg)/antagonist (H 1 : cetirizine 0.1 µg) and (H 2 : ranitidine: 50 µg)]. Results indicate that mice treated with diazepam at doses 1, 2 mg/kg, i.p. significantly increased the brain histamine levels. Moreover, in mice pretreated with histaminergic transmission-enhancing agents, the diazepam (2 mg/kg, i.p.)-induced motor incoordination was significantly reversed. Contrastingly, diazepam (1 mg/kg, i.p.) in its subeffective dose produced significant motor deficits in mice preintracerebroventricular injected with histamine H 1 and H 2 receptor antagonists on both the employed tests. Therefore, it is postulated that endogenous histamine operates via H 1 and H 2 receptor activation to alleviate the motor-impairing effects of diazepam.

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刺激中枢组胺能传导可减轻地西泮引起的小鼠轱辘杆和横梁行走试验的运动障碍。
研究表明,服用地西泮会影响涉及运动行为的多个脑区的组胺释放。因此,本研究使用rota-rod和横梁行走试验,探讨了中枢组胺能系统在地西泮诱导的小鼠运动能力缺陷中可能发挥的调节作用。本研究评估了不同剂量地西泮(0.5、1、2和3毫克/千克,静脉注射)对小鼠在轮杆和横梁行走试验中运动表现的影响。此外,还测定了地西泮给药后的脑组胺水平,并评估了地西泮诱导的小鼠运动障碍,这些小鼠经中枢(脑室内)预处理后使用了组胺能药物,如组胺(0.1、10 µg)、组胺前体(L-组氨酸:0.1,2.5 µg)、组胺神经元释放剂/H3 受体拮抗剂(硫普酰胺:0.5,10 µg)、H1 和 H2 受体激动剂[2-(3-三氟甲基苯基)组胺(FMPH:0.1,6.5 µg;氨茶碱:0.1,5 µg)/拮抗剂(H1:西替利嗪 0.1 µg)和(H2:雷尼替丁:50 µg)]。结果表明,以 1、2 毫克/千克的剂量给小鼠静脉注射地西泮会显著增加脑组胺水平。此外,在使用组胺能传递增强剂预处理的小鼠中,地西泮(2 毫克/千克,静注)诱导的运动不协调被明显逆转。相反,在小鼠脑室注射组胺 H1 和 H2 受体拮抗剂前,次有效剂量的地西泮(1 毫克/千克,静注)会在两种测试中产生明显的运动障碍。因此,可以推测内源性组胺是通过激活 H1 和 H2 受体来减轻地西泮的运动损伤作用的。
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
Behavioural Pharmacology
Behavioural Pharmacology 医学-行为科学
CiteScore
3.40
自引率
0.00%
发文量
84
审稿时长
6-12 weeks
期刊介绍: Behavioural Pharmacology accepts original full and short research reports in diverse areas ranging from ethopharmacology to the pharmacology of schedule-controlled operant behaviour, provided that their primary focus is behavioural. Suitable topics include drug, chemical and hormonal effects on behaviour, the neurochemical mechanisms under-lying behaviour, and behavioural methods for the study of drug action. Both animal and human studies are welcome; however, studies reporting neurochemical data should have a predominantly behavioural focus, and human studies should not consist exclusively of clinical trials or case reports. Preference is given to studies that demonstrate and develop the potential of behavioural methods, and to papers reporting findings of direct relevance to clinical problems. Papers making a significant theoretical contribution are particularly welcome and, where possible and merited, space is made available for authors to explore fully the theoretical implications of their findings. Reviews of an area of the literature or at an appropriate stage in the development of an author’s own work are welcome. Commentaries in areas of current interest are also considered for publication, as are Reviews and Commentaries in areas outside behavioural pharmacology, but of importance and interest to behavioural pharmacologists. Behavioural Pharmacology publishes frequent Special Issues on current hot topics. The editors welcome correspondence about whether a paper in preparation might be suitable for inclusion in a Special Issue.
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