The effects of orexin-A and orexin receptors on anxiety- and depression-related behaviors in a male rat model of post-traumatic stress disorder.

Orexin neurons play an important role in stress-related mental disorders including post-traumatic stress disorder (PTSD). Anxiety- and depression-related symptoms commonly occur in combination with PTSD. However, the role of the orexin system in mediating alterations in these affective symptoms remains unclear. The medial prefrontal cortex (mPFC) is implicated in both cognitive and emotional processing. In the present study, we investigated anxiety- and depression-related behavioral changes using the elevated plus maze, the sucrose preference test, and the open field test in male rats with single prolonged stress (SPS) induced-PTSD. The expression of orexin-A in the hypothalamus and orexin receptors (OX1R and OX2R) in the mPFC was detected and quantified by immunohistochemistry, western blotting, and real-time polymerase chain reaction. We found that the SPS rats exhibited enhanced levels of anxiety, reduced exploratory activities, and anhedonia. Furthermore, SPS resulted in reductions in the expression of orexin-A in the hypothalamus and the increased the expression of OX1R in the mPFC. The intracerebroventricular administration of orexin-A alleviated behavioral changes in SPS rats and partly restored the increased levels of OX1R in the mPFC. These results suggest that the orexin system plays a role in the anxiety- and depression-related symptoms observed in PTSD.