Effects of altered neurotransmitter Glu and GABA on post-traumatic stress disorder in rats

Abstract

Objective: Investigate the role of changes in glutamic acid (Glu), gamma-aminobutyric acid (GABA), and imbalances in Glu-to-GABA ratio (GGR) in the pathogenesis of post-traumatic stress disorder (PTSD).

Methods: Male Sprague-Dawley rats were randomly assigned to four groups: control, PTSD, PTSD+monosodium glutamate (MSG), and PTSD+lamotrigine (LTG). The PTSD model was established using the single prolonged stress (SPS) method. Rats in the PTSD+MSG and PTSD+LTG groups received MSG and LTG via gavage, respectively. At weeks 1, 2, and 4 after successful PTSD modeling, the Morris water maze (MWM) test and open field test (OFT) were conducted. Concurrently, serum concentrations of corticosterone (CORT), epinephrine, brain-derived neurotrophic factor (BDNF), Glu, and GABA were measured. Moreover, the changes of Glu, GABA and Calcium/calmodulin-dependent protein kinase II (CAMK II) in the hippocampus were also determined.

Results: In the PTSD+MSG group, the GGR in both serum and hippocampus was elevated, whereas in the PTSD+LTG group, it was decreased. In the PTSD+LTG group, the content of CAMK II in the hippocampal tissue of rats was significantly increased (p < 0.01), while serum CORT and BDNF levels were reduced (p < 0.05). The change of GGR can affect the learning and spatial memory abilities, the level of spontaneous activity and the blood biochemical indexes of rats with PTSD.

Conclusion: Significant alterations in the GGR reflect neurotransmitter imbalances, which can influence the pathophysiology of PTSD. Targeted neurotransmitter supplementation or antagonistic therapies may help alleviate PTSD symptoms.

Keywords: CAMK II; GGR; PTSD; Serum biochemistry; hippocampus.