Melatonin mediated antidepressant-like effect in the hippocampus of chronic stress-induced depression rats: Regulating vesicular monoamine transporter 2 and monoamine oxidase A levels

Eur Neuropsychopharmacol. 2016 Oct;26(10):1629-37. doi: 10.1016/j.euroneuro.2016.07.005. Epub 2016 Aug 4.


The hippocampus is sensitive to stress which activates norepinephrine terminals deriving from the locus coeruleus. Melatonin exerts positive effects on the hippocampal neurogenic process and on depressive-like behaviour. Thus, in the present study, an examination was made of the effect of chronic melatonin treatment on norepinephrine content, synthesis, uptake, vesicular transport and degradation in the hippocampus of rats exposed to CUMS. This entailed quantifying the norephinephrine, mRNA and protein levels of DBH, NET, VMAT 2, MAO-A and COMT. The results show that CUMS evoked prolonged immobility. Melatonin treatment decreased immobility in comparison with the placebo group, reflecting an antidepressant-like effect. Compared with the placebo group, a dramatic decrease in norepinephrine content, decreased VMAT2 mRNA and protein and increased MAO-A protein levels in the hippocampus of the CUMS rats were observed. However, no significant differences in the levels of DBH, NET, COMT mRNA and protein and MAO-A mRNA levels between the placebo and the stressed groups were found. The results showed the restorative effects of melatonin on the stress-induced decline in the norepinephrine content of the hippocampus. It was observed that melatonin treatment in the CUMS rats prevented the stress-induced decrease in VMAT2 mRNA and protein levels, whereas it reduced the increase of the mRNA of COMT and protein levels of MAO-A. Chronic treatment with melatonin failed to alter the gene expression of DBH or NET in the hippocampus of the CUMS rats. Additionally, the results show that melatonin enhances VMAT2 expression and norepinephrine storage, whilst it reduces norepinephrine degrading enzymes.

Keywords: Depression; Enzymes; Hippocampus; Melatonin; Norepinephrine; Transporters.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Catechol O-Methyltransferase / biosynthesis
  • Catechol O-Methyltransferase / genetics
  • Depression / drug therapy*
  • Depression / etiology
  • Depression / psychology
  • Dopamine beta-Hydroxylase / biosynthesis
  • Dopamine beta-Hydroxylase / genetics
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Male
  • Melatonin / pharmacology*
  • Monoamine Oxidase / biosynthesis*
  • Motor Activity / drug effects
  • Norepinephrine / biosynthesis
  • Rats
  • Rats, Wistar
  • Stress, Psychological / psychology*
  • Swimming / psychology
  • Vesicular Monoamine Transport Proteins / biosynthesis*


  • Antidepressive Agents
  • Slc18a2 protein, rat
  • Vesicular Monoamine Transport Proteins
  • Dopamine beta-Hydroxylase
  • Monoamine Oxidase
  • Catechol O-Methyltransferase
  • Melatonin
  • Norepinephrine