Effect of orexin and its antagonist on the organization of emotional and exploratory behavior of rats in a model of psychic trauma

BACKGROUND: A number of recent studies have revealed the role of orexins in regulating emotional behavior and emotional memory. The rationale for this role of orexin regulation is the close bi-directional interaction of orexin neurons with emotional structures of the brain, such as the bed nucleus of the stria terminalis, locus ceruleus, central and dorsomedial amygdala, hippocampus, medial prefrontal cortex. There is experimental and clinical evidence that an endogenous or induced deficiency of orexin effects accelerates the elimination of traumatic memory.

AIM: To study the effect of the OX1R Orexin Receptor Antagonist SB408124 and orexin on the emotional and exploratory behavior of animals after predator-induced stress.

MATERIALS AND METHODS: The experiments were made with 36 male Wistar rats, divided into 4 groups of 8 animals. Animals of 3 groups were exposed to single simulation of post-traumatic stress disorder by exposition with the indian python and subsequent death of one rat as a result of predator activity. The rats of 2 experimental groups received SB408124 OX1R antagonist in a dose of 20 µl of 0.1% solution and Orexin A in the same dose intranasally. The other animals received physiological solution in a dose of 20 µl intranasally. Behavior tests was made 7 days after the modeling of psychotrauma. A panel of behavioral tests was used: an elevated X-maze, an “open field” test, and an “resident–intruder” test. The obtained data were statistically processed using the Student t-test and ANOVA dispersion analysis. The differences were considered statistically significant at p < 0.01.

RESULTS: Orexin antagonist SB408124 showed anxiolytic effects. SB408124 showed anxiolytic properties in stressed rats. It restored the time spent in the light arm of the elevated X-maze to the intact level. In the open field test SB408124 increased (p < 0.01) the orientation behavior and reduced the frequency of freezing in stressed animals. Orexin A suppressed (p < 0,01) locomotor activity of animals in the open field. In the “resident–intruder” test in stressed animals SB408124 restored suppressed communication activity (p < 0,01). Orexin A reduced communicative behavior and increased aggression of animals.

CONCLUSIONS: The work shows a moderate anxiolytic action of SB408124 in the post-traumatic stress model in rats.