Reversal of Schizophrenia-like Symptoms and Cholinergic Alterations by Melatonin

Arch Med Res. 2019 Jul;50(5):295-303. doi: 10.1016/j.arcmed.2019.08.005. Epub 2019 Oct 7.

Abstract

Background: Melatonin is a neurohormone that is linked to the pathogenesis of schizophrenia. The aim of this study was to assess the potential of melatonin in attenuating MK-801 induced schizophrenia-like behavioral and brain neurotoxicity markers.

Methods: Swiss albino mice were assigned into three groups (n = 6). Animals were administered MK-801 (1 mg/kg/mL, i.p.). MK-801 treated animals were supplemented with melatonin (10 mg/kg/1 mL i.p.) 10 min prior to MK-801 injection. The relative degrees of modulation of induced behaviors by melatonin were assessed in the open field, elevated plus maze, grip strength and rota rod. The changes in neurotoxicity enzymes and neuronal activity (c-fos) were demonstrated in this study.

Results: MK-801 injection effected normal open-field behaviors, c-fos expression, motor coordination and muscular strength. Melatonin was able to reduce the histological changes in the prefrontal cortex of mice brain.

Conclusion: Our data demonstrated that the treatment with melatonin attenuates the schizophrenic like symptoms in the mice having a protective effect on prefrontal cortex region of brain by mitigating the alteration of neurotoxicity markers. The protective effect of the treatment was shown to reduced elevation of AChE, c-fos expression and histopathological alterations.

Keywords: Cholinergic changes; Coginitive impairment; Dopamine; Melatonin; Mk-801; Schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholinergic Agents / pharmacology
  • Cholinergic Agents / therapeutic use*
  • Disease Models, Animal
  • Humans
  • Male
  • Melatonin / pharmacology
  • Melatonin / therapeutic use*
  • Mice
  • Schizophrenia / drug therapy*
  • Schizophrenia / pathology

Substances

  • Cholinergic Agents
  • Melatonin