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Melatonin alleviates PTSD-like behaviors and restores serum GABA and cortisol levels in mice

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Abstract

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.

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Funding

This work was supported by the scientific research funds of Wenzhou Science and Technology Bureau (Y2020244), Zhejiang Provincial Natural Science Foundation of China (LQ22H090008), Wenzhou Medical University (89421025), and National Innovation and Entrepreneurship Training Programs for College Students (202110343017).

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Author notes

  1. Zixuan Xu, Wen Li and Yixin Sun contributed equally to this work.

Authors and Affiliations

  1. School of Mental Health, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China

    Zixuan Xu, Wen Li, Yixin Sun, Wen Jin, Li Yu & Qi Wang

  2. School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China

    Jingyuan Yang

  3. Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China

    Qi Wang

  4. Key Laboratory of Alzheimer’s Disease of Zhejiang Province, Wenzhou, Zhejiang, China

    Qi Wang

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  1. Zixuan Xu
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  2. Wen Li
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  3. Yixin Sun
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  4. Wen Jin
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  5. Li Yu
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  6. Jingyuan Yang
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Contributions

The study was designed by Qi Wang and Jingyuan Yang. Material preparation, experiment execution, data collection, and analysis were performed by Zixuan Xu, Wen Li, Yixin Sun, Wen Jin, and Li Yu. The first draft of the manuscript was written by Qi Wang and Jingyuan Yang. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jingyuan Yang or Qi Wang.

Ethics declarations

This research was approved by the Ethical Committees of Animal Experimentation of Wenzhou Medical University. All experimental protocols complied with the Guide for the Care and Use of Laboratory Animals of Wenzhou Medical University.

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The authors declare no competing interests.

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Xu, Z., Li, W., Sun, Y. et al. Melatonin alleviates PTSD-like behaviors and restores serum GABA and cortisol levels in mice. Psychopharmacology 240, 259–269 (2023). https://doi.org/10.1007/s00213-023-06312-y

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