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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Neuropharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1451895
This article is part of the Research Topic Neuropharmacological Intervention for Severe Mental Illness and Suicide Prevention View all 7 articles

Restraint stress effects on glutamate signaling proteins level in the rats' frontal cortex; does β1 adrenoceptors activity matter?

Provisionally accepted
Agnieszka Zelek-Molik Agnieszka Zelek-Molik 1*Anna Gądek-Michalska Anna Gądek-Michalska 2Michał Wilczkowski Michał Wilczkowski 1Adam Bielawski Adam Bielawski 1Katarzyna Maziarz Katarzyna Maziarz 1Grzegorz Kreiner Grzegorz Kreiner 1Irena Maria Nalepa Irena Maria Nalepa 2
  • 1 Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
  • 2 Department of Physiology, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

The final, formatted version of the article will be published soon.

    Stress-evoked dysfunctions of the frontal cortex (FC) are correlated with changes in the functioning of the glutamatergic system, and evidence demonstrates that noradrenergic transmission is an important regulator of this process. In the current study, we adopted a restraint stress (RS) model in male Wistar rats to investigate whether the blockade of β1 adrenergic receptors (β1AR) with betaxolol (BET) in stressed animals influences the body's stress response and the expression of selected signaling proteins in the medial prefrontal cortex (mPFC). The study was divided into two parts. In the first part, rats were exposed to RS for 3, 7, or 14 days, and the expression of glutamate signaling proteins (p(S845)/t GluA1, p(Y1472)/t GluN2B, VGLUT1, VGLUT2) in the FC was analyzed to determine the optimal RS duration for studying mechanisms of hypofrontality. In the second part, rats were exposed to RS for 14 days, and BET (5 mg/kg, p.o.) was administered during the last 8 days immediately after RS. The body's stress reaction was assessed by analyzing body weight and blood levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT). Behavioral responses were evaluated using the Novel Object Recognition (NOR) and Elevated Plus Maze (EPM) tests. The impact of RS and BET on the expression of p(Y530)/t Fyn and p(S133)/t CREB in the mPFC was measured via Western blotting. The first part of the study demonstrated a decreased level of glutamate receptors in rats exposed to 14 days of RS, following an initial increase observed after 7 days of RS. Results from the second part revealed that chronic RS reduced body weight, impaired recognition memory in the NOR test, augmented blood levels of ACTH, and increased the expression of p(Y530)Fyn in the mPFC. However, β1AR blockade did not alter the effects of RS on weight gain, cognitive function, or the expression of p(Y530)Fyn. β1AR blockade normalized only the blood concentration of ACTH. These results suggest that decreased Fyn kinase activity, indicated by phosphorylation at Y530, underlies the stress-evoked downregulation of GluN2B in the FC in a manner independent of β1AR activity.

    Keywords: ACTH, Betaxolol, elevated plus maze, frontal cortex, Fyn kinase, restraint stress, glutamate receptors, Novel object recognition

    Received: 20 Jun 2024; Accepted: 04 Dec 2024.

    Copyright: © 2024 Zelek-Molik, Gądek-Michalska, Wilczkowski, Bielawski, Maziarz, Kreiner and Nalepa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Agnieszka Zelek-Molik, Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland

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