Rationale: Melatonin is an endogenous hormone which modulates sleep-wake cycles. Previous studies have found a close correlation between melatonin and post-traumatic stress disorder (PTSD), a trauma- and stress-related psychiatric disorder with symptoms of sleep disturbance. However, it is still unclear if melatonin can have a therapeutic effect on PTSD.
Objective: This study aimed to investigate the effects of melatonin on foot shocks induced PTSD-like behaviors and abnormal neuroendocrine levels in mice.
Results: As compared to no-shock controls, PTSD-like mice spent significantly more time freezing and displayed less rearing in a contextual fear test, spent significantly less time in and had fewer entries into open arms in an elevated maze test, and spent significantly less time in and had fewer entries into a light box in a light-dark transition task. In addition, serum GABA and cortisol levels were both found to be significantly decreased, whereas epinephrine levels were significantly increased in the PTSD-like mice. Our results showed that intraperitoneal injections of melatonin (2 mM, but not 0.2 nor 20 mM, 0.1 ml/day for two consecutive weeks) alleviated PTSD-like behaviors and restored serum GABA and cortisol levels. Further, it was found that melatonin receptor 1/2 antagonist luzindole significantly blocked the beneficial effects of melatonin for PTSD-like behaviors and serum GABA and cortisol levels, whereas melatonin receptor 2 antagonist 4-P-PDOT slightly blocked these effects.
Conclusions: These results indicate that melatonin has a potential therapeutic effect on PTSD-like symptoms in mice, and melatonin receptor 1 mediated the effect.
Keywords: Cortisol; GABA; Melatonin; Melatonin receptor; PTSD.
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.