{"title":"Dual effects of anandamide in the antiepileptic activity of diazepam in pentylenetetrazole-induced seizures in mice.","authors":"Shyamshree S S Manna","doi":"10.1097/FBP.0000000000000700","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8832,"journal":{"name":"Behavioural Pharmacology","volume":"33 8","pages":"527-541"},"PeriodicalIF":1.6000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Behavioural Pharmacology","FirstCategoryId":"102","ListUrlMain":"https://doi.org/10.1097/FBP.0000000000000700","RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
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.
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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