Mechanisms of Memory Impairment Induced by Orexin-A Via Orexin 1 and Orexin 2 Receptors in Post-traumatic Stress Disorder Rats

Post-traumatic stress disorder (PTSD) patients exhibit abnormal learning and memory. Axons from orexin neurons in the lateral hypothalamus innervate the hippocampus, modulating learning and memory via the orexin 1 and 2 receptors (OX1R and OX2R). However, the role of the orexin system in the learning and memory dysfunction observed in PTSD is unknown. This was investigated in the present study using PTSD animal model-single prolonged stress (SPS) rats. Spatial learning and memory in the rats were evaluated with the Morris water maze (MWM) test; changes in body weight and food intake were recorded to assess changes in appetite; and the expression of orexin-A and its receptors in the hypothalamus and hippocampus was examined and quantified by immunohistochemistry, western blotting and real-time PCR. The results showed that spatial memory was impaired and food intake was decreased in SPS rats; this was accompanied by downregulation of orexin-A in the hypothalamus and upregulation of OX1R and OX2R in the hippocampus and of OX1R in the hypothalamus. Intracerebroventricular administration of orexin-A improved spatial memory and enhanced appetite in SPS rats and partly reversed the increases in OX1R and OX2R levels in the hippocampus and hypothalamus. These results suggest that the orexin system plays a critical role in the memory and appetite dysfunction observed in PTSD.