Orexinergic system and acquisition of conditional fear memory in male PTSD rats

The remarkable feature of PTSD is changes in structure and function of the brain, especially the most important structures are medial prefrontal, hippocampus and amygdala. Orexinergic neurons that located in lateral hypothalamus carry extensive projections to these areas. The Orexinergic system is involved in the acquisition of fear memories. The aim of this study is to investigate the role of this system in acquisition of fear memory in PTSD rats. In this study the wistar rats were implanted with bilateral cannula in the amygdala for micro- injection of orexin receptor-1 antagonist (SB334867), orexin receptor-2 antagonist (TCSOX229), the solvent of SB334867 and the solvent of TCSOX229, respectively in 4 experimental groups; SB, TC, SB control and TC 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 then immediately after the shock they received microinjection of drugs. The day after, the freezing behavior, as an indicator of memory extinction, was evaluated in 3 continuous days. Control rats showed a freezing of 80 to 90 percent in the first extinction test. This percent dropped by about 70 in the third test. SB334867 and TCSOX229 significantly decreased the freezing behavior in SB, TC groups as compared with SB control and TC control groups respectively. This decrease was sustained in all three consecutive tests. Decreasing in freezing behavior in memory tests indicates the formation of memory extinction in PTSD rats and since antagonists were injected before conditioning, this effect applies through interference with the acquisition of fear memory. Findings of this study verified the role of orexin receptors 1 and 2 in acquisition of contextual fear memory in PTSD rats and that inhibition of this system results in fear extinction.

کلیدواژه ها:

Post-traumatic Stress disorder ، Extinction ، Acquisition ، Orexin ، Amygdala