Abstract
Recently the role of the orexin system in the learning and memory, especially orexin A, which could enhance fear memory through regulating the activity of amygdala, has drawn considerable attention. However, the relationship between orexin A and extinction memory remains unclear. To investigate the effect of orexin A on extinction memory in humans, we recruited 43 male subjects and divided them into a recent group and remote group. After acquiring Pavlovian fear conditioning, individuals in recent group experienced fear extinction 24 h after acquisition, and remote group underwent extinction 2 weeks later. Meanwhile, plasma orexin A levels before extinction were measured by enzyme-linked immunosorbent assay. Both groups received memory test 24 h after fear extinction. The results showed that both recent and remote groups successfully acquired fear conditioning and had spontaneous recovery at test. In particular, the correlational analysis indicated that orexin A levels before extinction were negatively associated with fear responses during test only in recent group, but not in remote group. Moreover, individuals with high orexin A levels still kept low fear responses after extinction in recent group by subgroup analyses. The results suggest that orexin A could influence the retention of recent fear memory extinction, without affecting remote fear extinction. These findings remind us the orexin system can be a potential treatment target for fear-related disorders, and the mechanisms of recent and remote fear extinction may be different.
Highlights
Fear memory could help us to adapt for survival, since it guides individuals to avoid dangerous situations
No significant differences in age, level of education, height, weight, body mass index (BMI), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), Montreal Cognitive Assessment (MoCA), or shock intensity were observed between two groups by independent-sample t-tests, and the χ2 test showed that exercise frequencies were comparable between the two groups
The results are expressed as mean ± standard error of mean (SEM)
Summary
Fear memory could help us to adapt for survival, since it guides individuals to avoid dangerous situations. In clinic the first-line treatment for fear-related disorders is exposure therapy, which just temporally inhibits the original fear memory, Orexin A and Fear Extinction and the extinguished fear often returns when re-exposure to the traumatic events (reinstatement) and re-encountering the trauma associated cues out of the extinction environment (renewal), and after time passes by (spontaneous recovery) (Rescorla and Heth, 1975; Bouton and King, 1983; Quirk, 2002). This reminds us that investigating the mechanisms of fearrelated disorders and the influence factors of exposure therapy is essential for the prevention and treatment of fear-related disorders. Manipulations that enhance extinction are vital for improving the efficacy of exposure therapy
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