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Peculiarities of Fear Memory Extinction in Male and Female Disc1-Q31L Mice

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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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Funding

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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Authors and Affiliations

  1. Scientific Research Institute of Neurosciences and Medicine, Novosibirsk, Russia

    N. D. Chizhova, K. V. Smirnova, N. I. Dubrovina, A. V. Kalueff & T. G. Amstislavskaya

  2. Institute of Cytology and Genetics, Novosibirsk, Russia

    N. D. Chizhova & K. V. Smirnova

  3. Novosibirsk State University, Novosibirsk, Russia

    A. V. Kalueff & T. G. Amstislavskaya

  4. Sirius University of Science and Technology, Sochi, Russia

    A. V. Kalueff

  5. St. Petersburg State University, St. Petersburg, Russia

    A. V. Kalueff

  6. Ural Federal University, Yekaterinburg, Russia

    A. V. Kalueff

Authors
  1. N. D. Chizhova
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  2. K. V. Smirnova
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  3. N. I. Dubrovina
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  4. A. V. Kalueff
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  5. T. G. Amstislavskaya
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Contributions

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.

Corresponding authors

Correspondence to N. D. Chizhova or K. V. Smirnova.

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ETHICS APPROVAL

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).

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest.

Additional information

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

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