Abstract
Depressive disorders are common psychopathologies highly comorbid with other mental diseases, especially post-traumatic stress disorder, with overt gender differences in susceptibility. The Disc1-Q31L mutant mice are characterized by depression-like behavior and disrupted molecular pathways involved in fear memory. Here, we assess the sex- and strain differences in learning and extinction of a conditioned passive avoidance response (CPAR) in male and female Disc1-Q31L mice vs. control C57BL/6 mice. Overall, male and female mice of both strains learned equally well but differed in fear memory extinction, i.e. the ability to form a new safety memory trace in the dark compartment of the test apparatus, previously associated with aversion. C57BL/6 female mice revealed poorer CPAR extinction than males, while both sexes showed strain differences in the extinction dynamics. While Disc1-Q31L male mice reached total extinction later than C57BL/6 males, Disc1-Q31L females exhibited no extinction throughout all 24 testing days. Collectively, this not only supports the role of Disc1 in fear memory extinction but also shows sex-dependent impact of its Q31L mutation in this process.
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This work was supported by budgetary funding for basic scientific research at the Scientific Research Institute of Neurosciences and Medicine (No. 122042700001-9). No additional grants for this research project were obtained.
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N.I.D.—experimental design and data collection, N.D.Ch., K.V.S.—data processing and writing the manuscript, A.V.K., T.G.A.—discussing the results and writing the article.
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Animal experiments were performed in full compliance with the NIH Guidelines for the care and use of laboratory animals (http://oacu.od.nih.gov/regs/index.htm), the requirements of the Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals used for scientific purposes, and a Guide to Good Laboratory Practice approved by the Ministry of Health and Social Development of the Russian Federation (Order No. 708n of August 23, 2010).
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Translated by A. Polyanovsky
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Russian Text © The Author(s), 2023, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2023, Vol. 109, No. 12, pp. 1898–1907https://doi.org/10.31857/S0869813923120038.
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Chizhova, N.D., Smirnova, K.V., Dubrovina, N.I. et al. Peculiarities of Fear Memory Extinction in Male and Female Disc1-Q31L Mice. J Evol Biochem Phys 59, 2338–2345 (2023). https://doi.org/10.1134/S0022093023060340
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DOI: https://doi.org/10.1134/S0022093023060340