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• W2068541019 abstract "The promise of subtype-selective GABAA receptor drugs with anxiolytic properties but with a much reduced side-effect burden (compared to benzodiazepines) is an attainable goal. However, its achievement necessitates the availability of in vivo preclinical assays capable of demonstrating differences as well as similarities between subtype-selective agents and non-selective benzodiazepines. In this study, we have compared three mouse strains (NMRI, C57BL/6J and DBA/2) in four models of anxiety-like behaviour (plus-maze, zero-maze, light–dark, and Vogel conflict). Furthermore, in each model, we have contrasted in detail the behavioural responses of each strain to the non-selective benzodiazepine chlordiazepoxide (CDP; 5–20 mg/kg), and the subtype-selective agents L-838,417 (GABAA-α2/3/5; 3–30 mg/kg) and zolpidem (GABAA-α1; 0.3–3.0 mg/kg). The data show a complex mouse strain × model × pharmacological agent interaction. Most importantly, not all mouse strain × model test systems showed a positive response to CDP or predicted the response to L-838,417. This dissociation between CDP and L-838,417 opens up opportunities for preclinical test systems that differentiate subtype-selective and non-selective GABAA receptor agents, an attribute that might well be important in providing the necessary confidence for further drug development. Present findings suggest the need for a much greater focus on defining test systems appropriate for screening novel chemical entities, rather than self-selection of models or genotypes based on responses to known pharmacological agents. For example, if current data with L-838,417 are confirmed with compounds showing similar selectivity profiles, such agents may in future be best identified and characterised using test systems comprising NMRI mice in the zero-maze and/or C57 mice in the Vogel conflict and/or light–dark tests." @default.
• W2068541019 created "2016-06-24" @default.
• W2068541019 creator A5030355028 @default.
• W2068541019 creator A5048807123 @default.
• W2068541019 creator A5082790522 @default.
• W2068541019 date "2008-07-01" @default.
• W2068541019 modified "2023-10-03" @default.
• W2068541019 title "Strain- and model-dependent effects of chlordiazepoxide, L-838,417 and zolpidem on anxiety-like behaviours in laboratory mice" @default.
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• W2068541019 doi "https://doi.org/10.1016/j.pbb.2008.01.014" @default.
• W2068541019 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18321566" @default.
• W2068541019 hasPublicationYear "2008" @default.
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