Sex differences in the effects of chronic stress and oxycodone associative learning on glial markers in rat hippocampus.

Prior studies revealed significant sex differences in hippocampal opioid neuronal networks especially after chronic immobilization stress (CIS) that have important implications for opioid associative learning. Besides neurons, glia play important roles in hippocampal associated learning and can be affected by sex and environmental conditions. Here, we examined the relationship of sex and CIS on microglia (ionized calcium binding adapter molecule, Iba1) and astrocyte (glial fibrillary acidic protein, GFAP) densities in rat hippocampus following conditioned place preference (CPP) to saline (Sal) or oxycodone (Oxy). Although baseline glial densities were few, Sal females compared to Sal males had lower CA3b Iba1 and CA1. Following Oxy CPP, only females had increased Iba1 densities in CA3b and CA2/3a and GFAP densities in CA1, but both sexes had increased GFAP densities in CA3b. Moreover, compared to Sal counterparts, GFAP densities were lower in dentate gyrus (DG) in Oxy females and in CA1 in Oxy males. CIS females and males compared to unstressed counterparts had decreased CA3b Iba1 and GFAP densities and DG GFAP densities, however, these decreases were more extensive in males. Oxy CIS females, which acquired Oxy CPP, primarily had increased Iba1 and GFAP densities in CA1 and CA3 and decreased GFAP densities in DG. In contrast, Oxy CIS males, which did not acquire Oxy CPP, primarily exhibited increases in GFAP densities in the DG. These studies, together with our prior studies, reveal significant sex differences in the hippocampal glial densities, especially after CIS, which have important implications for Oxy associated learning processes.