Circadian modulation of neuroplasticity by melatonin: a target in the treatment of depression

Br J Pharmacol. 2018 Aug;175(16):3200-3208. doi: 10.1111/bph.14197. Epub 2018 Apr 17.


Mood disorders are a spectrum of neuropsychiatric disorders characterized by changes in the emotional state. In particular, major depressive disorder is expected to have a worldwide prevalence of 20% in 2020, representing a huge socio-economic burden. Currently used antidepressant drugs have poor efficacy with only 30% of the patients in remission after the first line of treatment. Importantly, mood disorder patients present uncoupling of circadian rhythms. In this regard, melatonin (5-methoxy-N-acetyltryptamine), an indolamine synthesized by the pineal gland during the night, contributes to synchronization of body rhythms with the environmental light/dark cycle. In this review, we describe evidence supporting antidepressant-like actions of melatonin related to the circadian modulation of neuroplastic changes in the hippocampus. We also present evidence for the role of melatonin receptors and their signalling pathways underlying modulatory effects in neuroplasticity. Finally, we briefly discuss the detrimental consequences of circadian disruption on neuroplasticity and mood disorders, due to the modern human lifestyle. Together, data suggest that melatonin's stimulation of neurogenesis and neuronal differentiation is beneficial to patients with mood disorders. LINKED ARTICLES: This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Circadian Rhythm / physiology*
  • Depression / drug therapy*
  • Depression / metabolism
  • Depression / physiopathology
  • Glutamic Acid / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Humans
  • Melatonin / physiology*
  • Melatonin / therapeutic use
  • Neuronal Plasticity / physiology*


  • Glutamic Acid
  • Melatonin