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dc.creatorDivljaković, Jovana
dc.creatorMilić, Marija
dc.creatorTimić, Tamara
dc.creatorSavić, Miroslav
dc.date.accessioned2019-09-02T11:28:11Z
dc.date.available2019-09-02T11:28:11Z
dc.date.issued2012
dc.identifier.issn1734-1140
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/1668
dc.description.abstractBackground: Behavioral effects of benzodiazepines following repeated exposure vary according to the intrinsic efficacy of the benzodiazepine studied, treatment schedule and the behavioral parameters evaluated. Methods: We applied the behavioral paradigms of spontaneous locomotor activity, elevated plus maze and grip strength to investigate the sedative, anxiolyfic and myorelaxant effect of acute challenge with 2 mg/kg diazepam administered after 14 days of protracted treatment with 0.5, 2 or 10 mg/kg of diazepam. In addition, we studied the effects of everyday handling and intraperitoneal (ip) administration on animal behavior. Results: Tolerance to the sedative effect of 2 mg/kg diszepam ensued after 14 days of protracted treatment with 2 and 10 mg/kg of diazepam. In contrast, treatment with the lowest dose (0.5 mg/kg) of diazepam resulted in potentiation of the sedative effect of acute challenge with 2 mg/kg diazepam thus confounding the detection of the anxiolytic effect of diazepam. A sensitization-like response to the anxiolytic action of 2 mg/kg diazepam was seen after protracted treatment with the intermediate dose (2 mg/kg); however, anxiolytic effect was absent after protracted administration of the highest dose. Partial tolerance to the muscle relaxant effect of 2 mg/kg diazepam ensued after protracted treatment with diazepam regardless of the dose. Daily handling or ip administration did not alter the behavioral response to acute challenge with 2 mg/kg diazepam in all the three behavioral paradigms studied. Conclusion: The presented results showed that behavioral effects of acute challenge with diazepam were differently affected by the dose administered during protracted treatment.en
dc.publisherPolish Acad Sciences Inst Pharmacology, Krakow
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175076/RS//
dc.rightsrestrictedAccess
dc.sourcePharmacological Reports
dc.subjectspontaneous locomotor activityen
dc.subjectelevated plus mazeen
dc.subjectgrip strengthen
dc.subjecttoleranceen
dc.titleTolerance liability of diazepam is dependent on the dose used for protracted treatmenten
dc.typearticle
dc.rights.licenseARR
dcterms.abstractСавић, Мирослав; Дивљаковић, Јована; Милић, Марија; Тимић, Тамара;
dc.citation.volume64
dc.citation.issue5
dc.citation.spage1116
dc.citation.epage1125
dc.citation.other64(5): 1116-1125
dc.citation.rankM22
dc.identifier.wos000208844100010
dc.identifier.doi10.1016/S1734-1140(12)70908-8
dc.identifier.pmid23238468
dc.identifier.scopus2-s2.0-84873737172
dc.identifier.rcubconv_1504
dc.type.versionpublishedVersion


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