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The ameliorative effect of midazolam on empathy-like behavior in old rats

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Abstract

Although studies suggest that cognitive functions in the elderly are impaired, elderly people tend to be more successful and wiser in solving emotional problems. In empathy-like behavior models, the observer rat rescues the distressed cage mate by displaying emotional and cognitive ability. The aim of the study was to investigate the changes in empathy-like behavior in older rats in comparison to adult rats. In addition, we wanted to determine the effects of alterations in neurochemicals (such as corticosterone, oxytocin, vasopressin, and their receptor levels) and emotional situations on this behavior. In our study, we initially completed empathy-like behavior tests and emotional tests (open field, elevated plus maze) and performed neurochemical examinations in the serum and brain tissues. In the second step of research, we applied a midazolam (benzodiazepine) treatment to examine the effect of anxiety on empathy-like behavior. In the old rats, we observed that empathy-like behavior deteriorated, and anxiety signs were more pronounced. We detected a positive correlation between the latency in empathy-like behavior and corticosterone levels and v1b receptor levels. The midazolam effect on empathy-like behavior was attenuated by flumazenil (a benzodiazepine receptor antagonist). The recordings of ultrasonic vocalization showed frequencies around 50 kHz emitted by the observer and this was associated with the expectation of social contact. Our results state that compared to adult rats, old rats were more concerned and failed during empathy-like behavior. Midazolam may improve this behavior by anxiolysis.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Physiology, School of Medicine, Dokuz Eylül University, Balçova, Izmir, Turkey

    Ferda Hosgorler, Erhan Caner Akkaya, Rabia Ilgin, Basar Koc & Nazan Uysal

  2. College of Vocational School of Health Services, Dokuz Eylül University, Izmir, Turkey

    Servet Kizildag

  3. School of Sport Sciences and Technology, Dokuz Eylül University, Izmir, Turkey

    Hikmet Gumus

Authors
  1. Ferda Hosgorler
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  2. Erhan Caner Akkaya
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  3. Rabia Ilgin
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  7. Nazan Uysal
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Contributions

Conceptualization: Ferda Hosgorler. Data curation: Ferda Hosgorler, Erhan Caner Akkaya, Rabia Ilgin, Servet Kizildag, Basar Koc. Formal analysis: Ferda Hosgorler, Erhan Caner Akkaya, Rabia Ilgin, Hikmet Gumus. Funding acquisition: Nazan Uysal. Investigation: Ferda Hosgorler, Erhan Caner Akkaya, Rabia Ilgin, Basar Koc, Servet Kizildag. Methodology: Ferda Hosgorler, Nazan Uysal. Resources: Nazan Uysal. Validation: all authors. Writing — original draft: Ferda Hosgorler. Writing — review and editing: all authors. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Ferda Hosgorler.

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Ethical approval

The study was approved by the Experimental Animals Ethics Committee (approval number: 05.04.2018-40/2018). The rats’ care and experimental procedures were performed by the experimental study team in accordance with the “Guide for the Care and Use of Laboratory Animals” guide.

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The authors declare no competing interests.

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Hosgorler, F., Akkaya, E.C., Ilgin, R. et al. The ameliorative effect of midazolam on empathy-like behavior in old rats. Naunyn-Schmiedeberg's Arch Pharmacol 396, 3183–3193 (2023). https://doi.org/10.1007/s00210-023-02526-1

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