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

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).

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.

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.

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.