Dual effects of anandamide in the antiepileptic activity of diazepam in pentylenetetrazole-induced seizures in mice.

IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES
Shyamshree S S Manna
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引用次数: 1

Abstract

The prototype endocannabinoid, anandamide activates both CB 1 and transient receptor potential vanilloid type 1 channels (TRPV1) receptor at different concentrations. At high concentrations, anandamide-mediated TRPV1 effects are opposite to its effects at low concentrations via CB 1 receptor. Thus, synaptic concentrations of anandamide govern the neuronal activity and consequently might affect the response of a drug. This study was undertaken to investigate the influence of high and low doses of anandamide on the anticonvulsant action of diazepam on the subcutaneous dose of pentylenetetrazole (PTZ) in Swiss mice weighing 20-25 g. Results revealed that intracerebroventricular administration of capsazepine (a TRPV1 antagonist: 1, 10, or 100 µg/mouse) and the low doses (10 µg/mouse) of anandamide, AM404 (anandamide transport inhibitor), or URB597 (fatty acid amide hydrolase inhibitor) augmented the anticonvulsant effect of diazepam. Conversely, higher dose of anandamide, AM404, URB597 (100 µg/mouse) as well as capsaicin (a TRPV1 agonist: 1, 10, or 100 µg/mouse) attenuated the protective effect of diazepam against PTZ-induced seizures. Thus, this study demonstrates that the effects of diazepam may be augmented by activating CB 1 receptors or dampened via TRPV1 receptors. The findings of the present study can be extrapolated to understand the use of TRPV1 blockers alone or in combination of benzodiazepines in the treatment of benzodiazepines-refractory status epilepticus, a condition associated with maladaptive trafficking of synaptic gamma-aminobutyric acid and glutamate receptors. However, potential clinical applications are needed to further support such preclinical studies.

阿南达胺对地西泮抗戊四唑致小鼠癫痫的双重作用。
作为内源性大麻素的原型,anandamide在不同浓度下激活cb1和瞬时受体电位香草素1型通道(TRPV1)受体。在高浓度下,阿南达胺介导的TRPV1效应与其通过cb1受体在低浓度下的效应相反。因此,突触内阿南达明的浓度控制着神经元的活动,从而可能影响药物的反应。本研究以体重20 ~ 25 g的瑞士小鼠皮下注射戊四唑(PTZ),研究高、低剂量阿南胺对地西泮抗惊厥作用的影响。结果显示,脑室内给药辣椒平(TRPV1拮抗剂:1、10或100µg/只小鼠)和低剂量(10µg/只小鼠)阿南达明、阿南达明转运抑制剂AM404或脂肪酸酰胺水解酶抑制剂URB597增强了地西泮的抗惊厥作用。相反,较高剂量的anandamide、AM404、URB597(100µg/只)以及辣椒素(TRPV1激动剂:1、10或100µg/只)会减弱地西泮对ptz诱导癫痫发作的保护作用。因此,本研究表明,地西泮的作用可能通过激活cb1受体而增强,或通过TRPV1受体而减弱。本研究的发现可以推断出TRPV1阻滞剂单独使用或与苯二氮卓类药物联合使用治疗苯二氮卓类药物难治性癫痫持续状态,这是一种与突触γ -氨基丁酸和谷氨酸受体的不适应运输相关的疾病。然而,潜在的临床应用需要进一步支持这些临床前研究。
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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