Selection for stress-induced analgesia affects the mouse hippocampal transcriptome

Stress responsiveness, including pain sensitivity and stress-induced analgesia (SIA), depends on genotype and, partially, is mediated by hippocampus. The present study examined differences in constitutive gene expression in hippocampus in lines of mice bred for high (HA) and low (LA) swim SIA. Between the lines, we found 1.5-fold or greater differences in expression of 205 genes in the hippocampus in nonstressed animals. The identity of these genes indicates that selective breeding for swim SIA affected many aspects of hippocampal neurons physiology, including metabolism, structural changes, and cellular signaling. Genes involved in calcium signaling pathway, including Slc8a1, Slc8a2, Prkcc, and Ptk2b, were upregulated in LA mice. In HA mice, robust upregulation of genes coding some transcription factors (Klf5) or receptors for neurotensin (Ntsr2) and GABA (Gabard) suggests the genetic basis for a novel mechanism of the non-opioid type of SIA in HA animals. Additional groups of differentially expressed genes represented functional networks involved in carbohydrate metabolism, gene expression regulation, and molecular transport. Our data indicate that selection for a single and very specific stress response trait, swim SIA, alters hippocampal gene expression. The results suggest that individual stress responsiveness may be associated with characteristics of the constitutive hippocampal transcriptome.