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The Early-Life «Programming» of Anxiety-Driven Behaviours in Adulthood as a Product of Predator-Driven Evolution


In mammals, a persistent increase in anxiety affects animal’s behavioral activities in adulthood consistently and might be “programmed” by early-life adverse events permanently. The “programming” of anxiety in adult subjects by severe neonatal events like cerebral hypoxia-ischemia or prolonged maternal separation is well established. By contrast, the age of onset of anxiety-related behavioral changes triggered by neonatal events of marginal intensity such as mild anoxia or a short-term exposure to glucocorticoids remains elusive to date. Here we studied anxiety-driven behaviors demonstrated in the elevated plus maze (EPM), in the marble burying (MB) and in the light–dark box (LDB) tests in adolescent and adult rats pre-exposed to an acute anoxic event and/or a single injection of synthetic glucocorticoid dexamethasone on postnatal day 2. Adult rats pre-exposed neonatally to hypoxia and dexamethasone demonstrated decreased activities either in the EPM or in the MB tests. Both exposures influenced anxiety-related activities as independent factors of similar strength, with additive impact on behaviors. In adolescent animals, the earliest behavioral changes detected after neonatal exposure to anoxia and glucocorticoids were found in the MB test at the age of one month. The findings evidenced that neonatal events of marginal intensity are capable of triggering a subsequent persistent increase in anxiety-driven behaviours in mammals, which might be detected in the adolescent age already. The identified within-generation early-life «programming» of mammalian anxiety by stress hormones and hypoxia might be considered as a possible product of prolonged predator-driven evolution and depicted like a signal-detection-theory payoff matrix.

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All data generated and analysed during this study are included in this published article and its supplementary information files.


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This study was supported by the RF Ministry of SHE budget project granted to ICG SB RAS program. Access to databases was provided by Novosibirsk State University, Novosibirsk State Technical University and Institute of Cytology and Genetics SB RAS. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Conceptualization: PNM, NND; Methodology: PNM, NND; Resources: PNM, NND; Investigation: PNM, AVB, NND; Formal analysis: PNM; Validation: AVB; Visualization: PNM; Project administration: PNM; Funding acquisition: NND; Supervision: NND; Writing—original draft: PNM, NND; Writing—review & editing: PNM, NND.

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Correspondence to Petr N. Menshanov.

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The authors declare that they have no conflict of interest.

Ethics Approval

All animal use procedures were in compliance with the European Directive 2010/63/EU and the National guidelines. The study was approved by the Bioethical Committee of the Institute of Cytology and Genetics SBRAS, Novosibirsk. All efforts were made to minimize animal suffering and to use only the number of animals necessary to produce the reliable data.

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Menshanov, P.N., Bannova, A.V. & Dygalo, N.N. The Early-Life «Programming» of Anxiety-Driven Behaviours in Adulthood as a Product of Predator-Driven Evolution. Evol Biol 49, 303–313 (2022).

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  • Hypoxia
  • Glucocorticoids
  • Anxiety
  • Neonatal “programming”
  • Adolescent
  • Payoff matrix