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Effects of Interferon-α on Depressive-Like Behavior and Brain Neurochemistry in Rats Housed in Standard and Overcrowding Conditions

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Abstract

Immunotherapy with interferon-α (IFN-α) is frequently associated with neuropsychiatric consequences, including depression. Mechanisms underlying adverse effects of IFN-α are not fully understood. This study was aimed to determine whether intranasal administration of IFN-α can provoke depression-like behavior in rats and whether overcrowding stress can interfere or amplify the effects of IFN-α. To achieve this aim, effects of human IFN-α in low (50 IU/kg) and medium (8000 IU/kg) doses on the forced swimming test behavior and monoamines and their metabolite content in the brain structures of Wistar rats housed in standard and overcrowding conditions were investigated. Depressive-like behavior (increased immobility) was observed in rats housed in standard conditions after treatment with both doses of human IFN-α, as well as in vehicle-treated rats housed in stressful, overcrowding conditions. In standard conditions, a low dose of IFN-α produced a subtle alteration in the metabolism of dopamine only in one of the brain structures analyzed (nucleus accumbens). The medium dose of IFN-α induced more drastic neurochemical alterations in a larger number of brain structures. Overcrowding led to some changes in monoamine and their metabolite levels similar to those observed after IFN-α treatment with the medium dose in the standard housing conditions. In the overcrowded conditions, in contrast to the standard ones, IFN-α treatment in both doses reduced depression-like behavior and normalized neurochemical alterations induced by overcrowding. The results suggest that the effect of IFN-α on depression-like behavior and brain neurochemistry depends on the ongoing emotional status of animals: whether they are in stressful (overcrowded) or non-stressful (normal) conditions.

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Funding

The study was prepared solely within the state assignment of Ministry of Education and Science of the Russian Federation for 2021–2023.

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Authors and Affiliations

  1. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Science, Moscow, Russia

    N. A. Loginova, E. V. Loseva & K. Yu. Sarkisova

  2. Research Zakusov Institute of Pharmacology, Moscow, Russia

    V. S. Kudrin

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  1. N. A. Loginova
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  2. E. V. Loseva
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  3. K. Yu. Sarkisova
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  4. V. S. Kudrin
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Contributions

N.A. Loginova: investigation, writing—original draft preparation. E.V. Loseva: conceptualization, investigation, writing—original draft preparation, writing—reviewing and editing. K.Yu. Sarkisova: writing—reviewing and editing, investigation, methodology. V.S. Kudrin: investigation.

Corresponding author

Correspondence to E. V. Loseva.

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ETHICS APPROVAL AND CONSENT TO PARTICIPATE

All procedures complied with the ethical standards approved by legal acts of the Russian Federation, the principles of the Basel Declaration, and by the Bioethics Committee of IHNA&NPh RAS (Minutes number 3 of 10.07.2020).

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Loginova, N.A., Loseva, E.V., Sarkisova, K.Y. et al. Effects of Interferon-α on Depressive-Like Behavior and Brain Neurochemistry in Rats Housed in Standard and Overcrowding Conditions. J Evol Biochem Phys 59, 2005–2021 (2023). https://doi.org/10.1134/S0022093023060108

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