Role of gut microbiota in the GBR12909 model of mania-like behavior in mice

Aline Silva de Miranda, Érica Leandro Marciano Vieira, Juliana dos Reis Bastos, Rodrigo Novaes Ferreira, Jacques R. Nicoli, Mauro Martins Teixeira, Leda Quercia Vieira, Fabrício A. Moreira, Antônio Lúcio Teixeira

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Growing evidence suggests a role for brain-gut-microbiota axis in affective disorders including major depression and bipolar disorder (BD). Herein, we aim to explore, by employing germ-free (GF) mice, the effect of the indigenous microbiota in the development of mania-like behavior. Conventional and GF mice were evaluated for the hyperlocomotion induced by the dopamine transporter inhibitor GBR12909 (15 mg/Kg), a validated model for mania-like behavior. Inflammatory mediators and neurotrophic factors were quantified in the prefrontal cortex, hippocampus and striatum. Mice lacking indigenous microbiota were less susceptible to the mania-like behavior induced by GBR12909. This effect was associated with decreased levels of inflammatory cytokines such as IL-6 and TNF-α, along with increased concentrations of anti- inflammatory cytokines (IL-10) and of neurotrophins (BDNF and NGF). We provided the first evidence that gut-microbiota-brain axis participates in the development of mania-like behavior in rodents, possibly through neuroimmunepathways.

Original languageEnglish (US)
Article number577292
JournalJournal of Neuroimmunology
StatePublished - Sep 15 2020
Externally publishedYes


  • Bipolar disorder
  • GBR12909
  • Gut-microbiota-brain axis
  • Inflammation
  • Mania
  • Neurotrophic factors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology


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