Figure 4.

Hippocampal mRNA levels of receptors involved in negative regulation of the HPA axis were evaluated in response to neonatal maternal separation (NMS) and water avoidance stress (WAS). A) Exposure to WAS significantly decreased the hippocampal mRNA level of corticotropin-releasing factor receptor 1 (CRF₁) overall, as well as in NMS mice at 1d and 8d post-WAS compared to baseline (BL) levels. B) NMS similarly decreased overall hippocampal mRNA levels of CRF receptor 2 (CRF₂), however, WAS exposure caused a transient and significant decrease in in NMS hippocampus at 1d post-WAS, compared to naïve, and a significant increase in CRF₂ mRNA levels in both naïve and NMS hippocampus at 8d post-WAS compared to their respective BL and 1d post-WAS levels. C) The hippocampal mRNA levels of glucocorticoid receptor (GR) was significantly impacted by NMS and an NMS/WAS interaction, particularly at 1d post-WAS. D) Mineralocorticoid receptor (MR) mRNA levels were significantly affected by WAS and an NMS/WAS interaction, resulting in a transient decrease in expression at 1d post-WAS in NMS mice and a return to BL levels at 8d post-WAS. E) Despite a slight reduction at 1d post-WAS in NMS mice, no significant effects of NMS or WAS were observed on the hippocampal mRNA levels of brain-derived neurotrophic factor (BDNF). Brackets indicate a significant effect of NMS (§ p < 0.05), WAS (†, †††† p < 0.05, 0.0001), or NMS/WAS interaction (& p < 0.05), two-way ANOVA; *, ** p < 0.05, 0.01 vs. naïve; #, ##, ###, #### p < 0.05, 0.01, 0.001, 0.0001 vs. BL; ‡‡, ‡‡‡, ‡‡‡‡ p < 0.01, 0.001, 0.0001 vs. 1d post-WAS; Bonferroni’s multiple comparisons test. N=3–5 for all groups/time points.