Implications for the Treatment of Memory Disorders in PTSD by TCSOX229

The inability to traumatic memory extinction is one of the cognitive impairments in patients with PTSD. Amygdala is one of the structuresthat interfere with stress effects on different steps of memory in these patients. The lateral hypothalamic oroxinergic neurons have extensive bipolar connections with amygdala. Therefore, the purpose of this study was to evaluate the role of orexin receptor 2 in facilitatingmemory extinction in PTSD. Materials and Methods: In this study, Wistar rats were cannula implanted, bilaterally, in the amygdala for microinjection of orexin receptor-2 antagonist (TCSOX229; TCS-, 30 nmol/ side) and the solvent of TCSOX229, respectively in2 experimental groups; TCS and TCS control groups. One week after the surgery, single prolonged stress (SPS) method used to develop PTSD in rats. A week later, rats were conditioned by receiving electrical foot shock in fear conditioning system. The day after, the freezing behavior, as an indicator of memory extinction, was evaluated in 4 consecutive days. Immediately after every freezing behavior test in first three days, they received microinjection of drugs. Results: The level of freezing did not change during the first test. However, in the two next tests, the amount of immobilization in the TCS group was significantly lower than that of control (P <0.001). In all tests, the rate of freezing incontrol group was about 70 to 80 percent, while in TCS group the freezing time decreased from 65 percent to 35 percent. Conclusion: Repeated injection of orexin-2 receptor antagonist into the amygdala of PTSD animals, immediately after the extinction tests, facilitated theprocess of memory extinction.