The Effect of NKCC1 Inhibitor Azosemide on Emotional Behaviors and Hippocampal GABA Levels in a Rat Model of Post-traumatic Stress Disorder

Sebahattin Karabulut; Sümeyra Koç; Ayşegül Öztürk

doi:10.17776/csj.1624998

TR EN

NKCC1 inhibitörü azosemid'in travma sonrası stres bozukluğu sıçan modelinde emosyonel davranış ve hipokampal GABA düzeyleri üzerindeki etkisi

Öz

Travma sonrası stres bozukluğu (TSSB), travmatik bir olaya maruz kaldıktan hemen sonra veya yıllar sonra ortaya çıkabilen bir anksiyete bozukluğudur. Kapsamlı araştırmalara rağmen, TSSB'nin etiyolojisi büyük ölçüde bilinmemektedir, ancak bozulmuş GABAerjik iletiminin hastalık sürecinde rol oynayabileceği düşünülmektedir. Tek bir uzun süreli stres (SPS) prosedürü kullanarak, sodyum-potasyum-klorür ko-taşıyıcı (NKCC1) inhibitörü olan azaosemidin sıçanlarda anksiyete ve hafıza ile ilgili davranışlar ve hipokampal GABA düzeyi üzerindeki etkisini belirlemeyi amaçladık. Davranış testleri açık alan testi ve pasif kaçınma testi ile gerçekleştirildi, hipokampal GABA düzeyleri ise ELISA ile belirlendi. Azosemid tedavisinin TSSB'li sıçanlarda emosyonel davranışları kısmen iyileştirdiğini ve hafıza performansını önemli ölçüde iyileştirdiğini, ancak tek bir uzun süreli stres maruziyetinin neden olduğu hipokampal GABA düzeylerindeki düşüşü etkilemediğini bulduk. Bu bulgular, azosemidin özellikle bilişsel eksiklikler olmak üzere TSSB semptomları için kısmi terapötik faydalar sunabileceğini düşündürmektedir. Ancak, bozukluğun çeşitli nörobiyolojik temellerini ele almak için multimodal yaklaşımların gerekliliğini vurgulamaktadırlar.

Anahtar Kelimeler

The Effect of NKCC1 Inhibitor Azosemide on Emotional Behaviors and Hippocampal GABA Levels in a Rat Model of Post-traumatic Stress Disorder

Abstract

Post-traumatic stress disorder (PTSD) is an anxiety disorder that can occur immediately or years after exposure to a traumatic event. Despite extensive research, the etiology of PTSD is largely unknown, but it is thought that impaired GABAergic transmission may play a role in the disease process. Using a single prolonged stress (SPS) procedure, we aimed to determine the effect of azosemide, a sodium-potassium-chloride cotransporter (NKCC1) inhibitor, on anxiety and memory-related behaviors and hippocampal GABA level in rats. Behavioral tests were performed by open field test and passive avoidance test, while hippocampal GABA levels were determined by ELISA. We found that azosemide treatment partially improved emotional behavior and significantly improved memory performance in rats with PTSD, without affecting the decline in hippocampal GABA levels induced by a SPS exposure. These findings suggest that azosemide may offer partial therapeutic benefits for symptoms of PTSD, particularly cognitive deficits. However, they underscore the necessity for multimodal approaches to address the various neurobiological underpinnings of the disorder.

Keywords

Supporting Institution

This study is funded by TUBITAK 2209-A Research Project Support Programme for Undergraduate Students

Project Number

1919B012305656

Ethical Statement

All procedures involving the animals were conducted with the approval of the Sivas Cumhuriyet University Animal Experiments Local Ethics Committee (Decision No: 65202830-050.04.04-72).

Thanks

We would like to thank the Sivas Cumhuriyet University, School of Medicine, CUTFAM Research Center, Sivas, Turkey, for providing the necessary facilities to conduct this study.

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Details

Primary Language

English

Subjects

Basic Pharmacology

Journal Section

Research Article

Authors

Sebahattin Karabulut ^*
0000-0002-3261-4125
Türkiye

Sümeyra Koç
0009-0004-7328-788X
Türkiye

Ayşegül Öztürk
0000-0001-8130-7968
Türkiye

Publication Date

June 30, 2025

Submission Date

January 22, 2025

Acceptance Date

May 13, 2025

Published in Issue

Year 2025 Volume: 46 Number: 2

DOI

https://doi.org/10.17776/csj.1624998

IZ

https://izlik.org/JA42YY44UT

Cite

RIS / Bibtex

APA

Karabulut, S., Koç, S., & Öztürk, A. (2025). The Effect of NKCC1 Inhibitor Azosemide on Emotional Behaviors and Hippocampal GABA Levels in a Rat Model of Post-traumatic Stress Disorder. Cumhuriyet Science Journal, 46(2), 268-273. https://doi.org/10.17776/csj.1624998