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Beta CCT as well as flumazenil prevent the diazepam withdrawal-induced anxiety in the elevated plus maze in rats
dc.creator | Divljaković, Jovana | |
dc.creator | Timić, Tamara | |
dc.creator | Milinković, Marija M. | |
dc.creator | Batinić, Bojan | |
dc.creator | van Linn, Michael | |
dc.creator | Cook, James M. | |
dc.creator | Savić, Miroslav | |
dc.date.accessioned | 2019-09-02T11:27:57Z | |
dc.date.available | 2019-09-02T11:27:57Z | |
dc.date.issued | 2012 | |
dc.identifier.issn | 1461-1457 | |
dc.identifier.uri | https://farfar.pharmacy.bg.ac.rs/handle/123456789/1661 | |
dc.description.abstract | Objective : Despite a half century of clinical use and the recognized potential of benzodiazepine dependence, the mechanisms under- lying benzodiazepine withdrawal remain insufficiently understood. The aim of the present study was to assess the influence of the non- selective antagonist (flumazenil) and the preferential a1-subunit selective antagonist (bCCt) on the anxiety level after diazepam with- drawal. Methods : The male Wistar rats were protractedly treated during 21 days with diazepam (2 mg/kg) or solvent. On the testing day, 24 hours after the last injection, animals from the diazepam-treated groups received either antagonist (flumazenil or bCCt) or solvent, and animals from the solvent-treated groups received solvent or diaze- pam. Twenty minutes after administration of treatment on the testing day, single animals were placed in the elevated plus maze in order to assess the level of anxiety. Results : Two-way ANOVA revealed that animals withdrawn from diazepam spent significantly less time on the open arms than control animals (p=0.023). One-way ANOVA, followed by post hoc test, re- vealed that administration of flumazenil (10 mg/kg) or bCCt (1.25, 5 or 20 mg/kg) reversed the diazepam withdrawal-induced anxiety (percentage of open arm time : p=0.003, p=0.032, p=0.031 and p=0.014 compared to the diazepam-withdrawn group, respectively). Concomitant administration of antagonists (10 mg/kg flumazenil, or 1.25, 5 or 20 mg/kg bCCt) induced an anxiolytic effect comparable to that observed after acutely administrated diazepam (percentage of open arm time : p=0.142, p=0.187, p=0.243 and p=0.290, respect- ively). Conclusion : The present study demonstrated that administration of the a1-selective antagonist bCCt or non-selective antagonist flumazenil could prevent the withdrawal-induced anxiety and also induce an anxiolytic-like effect. Moreover, presented results have suggested that mechanism of preventing the withdrawal-induced anxiety involves the antagonism at a1-containing GABAA receptors. | |
dc.publisher | Oxford Univ Press, Oxford | |
dc.rights | openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0/ | |
dc.source | International Journal of Neuropsychopharmacology | |
dc.title | Beta CCT as well as flumazenil prevent the diazepam withdrawal-induced anxiety in the elevated plus maze in rats | en |
dc.type | conferenceObject | |
dc.rights.license | BY-NC | |
dcterms.abstract | Батинић, Бојан; ван Линн, Мицхаел; Милинковић, Марија М.; Тимић, Тамара; Цоок, Јамес М.; Савић, Мирослав; Дивљаковић, Јована; | |
dc.citation.volume | 15 | |
dc.citation.issue | Supplement 1 | |
dc.citation.spage | 201 | |
dc.citation.epage | 201 | |
dc.citation.other | 15: 201-201 | |
dc.citation.rank | aM21 | |
dc.description.other | 28th CINP World Congress of Neuropsychopharmacology, Stockholm, Sweden, 3–7 June 2012 | |
dc.identifier.wos | 000209062500737 | |
dc.identifier.doi | 10.1017/S1461145712000508 | |
dc.identifier.fulltext | http://farfar.pharmacy.bg.ac.rs/bitstream/id/11552/bCCT_as_well_pub_2012.pdf | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_farfar_1661 | |
dc.type.version | publishedVersion |