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

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.