Prefrontal Cortex Neurochemical Changes in Single Prolonged Stress as a Model of Post-traumatic Stress Disorder: In Vivo Magnetic Resonance Spectroscopy at 9.4 T

Abstract

Purpose

Single prolonged stress (SPS) is an animal model of post-traumatic stress disorder (PTSD). Until now, it has not been known how PTSD develops from the first exposure to traumatic events and neurochemical differences between acute/single stress and PTSD-triggering stress. The object of this study is to determine neurochemical changes in prefrontal cortex of rats using in vivo proton magnetic resonance spectroscopy (1H-MRS) at 9.4 T.

Method and Materials

Male Sprague–Dawley rats (n = 11; mean body weight: 200–220 g) were used. The SPS was used in this study. Rats were restrained for 2 h and then immediately forced to swim for 20 min in water (20–24 C). After a 15 min recuperation period, rats were exposed to ether until anesthesia occurred. MRS was performed 30 min before SPS, 30 min after the stressors, 3 and 7 days after the stressors to investigate time-dependent changes on metabolites levels in the PFC. Acquisition of MRI/MRS was conducted at four time points using 9.4 T Agilent Scanner. Concentration of metabolites was quantified by LCModel. A one-way ANOVA test with Tukey's HSD post-hoc test was used for statistical analyses.

Results

The SPS resulted in altered absolute metabolite concentrations for GABA [F(3.0) = 1.450, P = 0.035], glutamate [F(3.0) = 3.417, P = 0.026], glutathione [F(3.0) = 3.759, P = 0.018], NAA [F(3.0) = 3.919, P = 0.015], total choline [F(3.0) = 7.584, P = 0.000], total NAA [F(3.0) = 3.760, P = 0.018], total creatine [F(3.0) = 3.248, P = 0.032] and glutamine/glutamate [F(3.0) = 3.552, P = 0.023] among the four time points.

Conclusion

PTSD in human is associated with decreased neuronal activity in the PFC. In this study, SPS decreased glutamate (excitatory) and total choline (membrane turnover) on day 7.

Disclosure of interest

The authors have not supplied their declaration of competing interest.