Daily consumption of methylene blue reduces attentional deficits and dopamine reduction in a 6-OHDA model of Parkinson's disease

Neuroscience. 2017 Sep 17:359:8-16. doi: 10.1016/j.neuroscience.2017.07.001. Epub 2017 Jul 8.


Recently, alternative drug therapies for Parkinson's disease (PD) have been investigated as there are many shortcomings of traditional dopamine-based therapies including difficulties in treating cognitive and attentional dysfunction. A promising therapeutic avenue is to target mitochondrial dysfunction and oxidative stress in PD. One option might be the use of methylene blue (MB), an antioxidant and metabolic enhancer. MB has been shown to improve cognitive function in both intact rodents and rodent disease models. Therefore, we investigated whether MB might treat attentional deficits in a rat model of PD induced by 6-hydroxydopamine (6-OHDA). MB also has neuroprotective capabilities against neurotoxic insult, so we also assessed the ability of MB to provide neuroprotection in our PD model. The results show that MB could preserve some dopamine neurons in the substantia nigra par compacta when 6-OHDA was infused into the medial forebrain bundle. This neuroprotection did not yield a significant behavioral improvement when motor functions were measured. However, MB significantly improved attentional performance in the five-choice task designed to measure selective and sustained attention. In conclusion, MB might be useful in improving some attentional function and preserving dopaminergic cells in this model. Future work should continue to study and optimize the abilities of MB for the treatment of PD.

Keywords: 6-OHDA; disengagement behavior; methylene blue; neuroprotection; selective and sustained attention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Attention / drug effects*
  • Behavior, Animal
  • Dopamine / metabolism
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / metabolism*
  • Male
  • Methylene Blue / administration & dosage*
  • Neuroprotective Agents / administration & dosage*
  • Parkinsonian Disorders / drug therapy
  • Parkinsonian Disorders / metabolism*
  • Parkinsonian Disorders / psychology*
  • Rats, Sprague-Dawley
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Tyrosine 3-Monooxygenase / metabolism
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / metabolism


  • Antioxidants
  • Neuroprotective Agents
  • Tyrosine 3-Monooxygenase
  • Methylene Blue
  • Dopamine