Post-traumatic stress disorder (PTSD) is a serious debilitating condition with chronic course and limited available treatment options. There is a growing need to identify the molecular mechanisms of PTSD for new therapy exploration. We evaluated PTSD-induced gene expression changes in the amygdalae and hippocampi of Sprague-Dawley rats and the effects of Pregabalin (PGB), a gabapentin derivative of γ-aminobutyric acid (GABA). The rats were assigned into six experimental groups: control vehicle, control PGB, control naïve, PTSD vehicle, PTSD Pre-PGB (prophylactic), and PTSD Post-PGB (non-prophylactic). Amygdalae and hippocampi tissue samples were analyzed for changes in gene expression. One-way analysis of variance (ANOVA) was used to detect significant differences between groups in the amygdalae and hippocampi. Of the 88 genes examined, 65 genes in the amygdalae and 61 genes in the hippocampi had a large effect size greater than 0.18. Of these, the expression of Adora2aR gene, Cacna1a gene, Grin2c gene, Grm4 and Grm5 genes, Slc17a7 gene, Itpr1 gene, Slc32a1 gene, Slc6a12 and Slc6a13 genes were significantly down-regulated in the amygdalae of rodents that suffered PTSD. PGB prophylactic treatment prevented the down-regulation of gene expression of Cacna1a1, Grin2c, Grm5 and Itpr1 and their expression levels returned to amygdalae control levels. PGB-post PTSD treatment rescued the gene expression of Grin2c, Grm4, Grm5 and Slc32a1 back to amygdalae control levels. The expression of Cacna1a gene, Grm2 gene, Grm5 gene, Grm8 gene, Slc1a6 gene, Slc17a7 gene, Slc32a1 gene, Slc6a12 gene, and Slc6a13 gene was significantly decreased in the PTSD vehicle group of the hippocampi. Only PGB prophylactic treatment returned Cacna1a and Slc32a1 gene expression to the hippocampi control levels. Glutamate receptors, glutamate transporters, and GABA transporters play important roles in normal neural plasticity and in pathological conditions; our results suggest that optimized dose and length of Pregabalin administration may be developed into a potential PTSD treatment.
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