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dc.creatorJoksimović, Srđan
dc.creatorDivljaković, Jovana
dc.creatorvan Linn, Michael
dc.creatorVaragić, Zdravko
dc.creatorBrajković, Gordana
dc.creatorMilinković, Marija M.
dc.creatorYin, Wenyuan
dc.creatorTimić, Tamara
dc.creatorSieghart, Werner
dc.creatorCook, James M.
dc.creatorSavić, Miroslav
dc.date.accessioned2019-09-02T11:37:15Z
dc.date.available2019-09-02T11:37:15Z
dc.date.issued2013
dc.identifier.issn0924-977X
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/2028
dc.description.abstractDespite significant advances in understanding the role of benzodiazepine (BZ)-sensitive populations of GABA A receptors, containing the α 1 , α 2 , α 3 or α 5 subunit, factual substrates of BZ-induced learning and memory deficits are not yet fully elucidated. It was shown that α 1 -subunit affinity-selective antagonist Β-CCt almost completely abolished spatial learning deficits induced by diazepam (DZP) in the Morris water maze. We examined a novel, highly (105 fold) α 1 -subunit selective ligand-WYS8 (0.2, 1 and 10mg/kg), on its own and in combination with the non-selective agonist DZP (2mg/kg) or Β-CCt (5mg/kg) in the water maze in rats. The in vitro efficacy study revealed that WYS8 acts as α 1 -subtype selective weak partial positive modulator (40% potentiation at 100nM). Measurement of concentrations of WYS8 and DZP in rat serum and brain tissues suggested that they did not substantially cross-influence the respective disposition. In the water maze, DZP impaired spatial learning (acquisition trials) and memory (probe trial). WYS8 caused no effect per se, did not affect the overall influence of DZP on the water-maze performance and was devoid of any activity in this task when combined with Β-CCt. Nonetheless, an additional analysis of the latency to reach the platform and the total distance swam suggested that WYS8 addition attenuated the run-down of the spatial impairment induced by DZP at the end of acquisition trials. These results demonstrate a clear difference in the influence of an α 1 subtype-selective antagonist and a partial agonist on the effects of DZP on the water-maze acquisition.en
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175076/RS//
dc.relationNIMH NIH HHS 46851
dc.rightsrestrictedAccess
dc.sourceEuropean Neuropsychopharmacology
dc.subjectDiazepamen
dc.subjectGABA A subtype selective liganden
dc.subjectTwo electrode voltage clampen
dc.subjectWater mazeen
dc.titleBenzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of α 1 GABA A receptorsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractБрајковић, Гордана; Цоок, Јамес М.; Милинковић, Марија М.; Варагић, Здравко; ван Линн, Мицхаел; Дивљаковић, Јована; Савић, Мирослав; Сиегхарт, Wернер; Тимић, Тамара; Yин, Wенyуан; Јоксимовић, Срђан;
dc.citation.volume23
dc.citation.issue5
dc.citation.spage390
dc.citation.epage399
dc.citation.other23(5): 390-399
dc.citation.rankaM21
dc.identifier.doi10.1016/j.euroneuro.2012.05.003
dc.identifier.scopus2-s2.0-84891597940
dc.identifier.rcubconv_4830
dc.type.versionpublishedVersion


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