Combined actions of blueberry extract and lithium on neurochemical changes observed in an experimental model of mania: exploiting possible synergistic effects

  • Luiza Spohr
  • Mayara Sandrielly Pereira Soares
  • Pathise Souto Oliveira
  • Bruna da Silveira de Mattos
  • Natália Pontes Bona
  • Nathalia Stark Pedra
  • Fernanda Cardoso Teixeira
  • Carlus Augustu Tavares do Couto
  • Vitor Clasen Chaves
  • Flávio Henrique Reginatto
  • Meibel Teixeira Lisboa
  • Anderson Schwingel Ribeiro
  • Claiton Leoneti Lencina
  • Francieli Moro Stefanello
  • Roselia Maria SpanevelloEmail author
Original Article


Bipolar disorder is a psychiatric disease characterized by recurrent episodes of mania and depression. Blueberries contain bioactive compounds with important pharmacological effects such as neuroprotective and antioxidant actions. The aim of this study was to investigate the effects of blueberry extract and/or lithium on oxidative stress, and acetylcholinesterase (AChE) and Na+, K+-ATPase activity in an experimental ketamine-induced model of mania. Male Wistar rats were pretreated with vehicle, blueberry extract (200 mg/kg), and/or lithium (45 mg/kg or 22.5 mg/kg twice daily) for 14 days. Between the 8th and 14th days, the animals also received an injection of ketamine (25 mg/kg) or vehicle. On the 15th day the animals received a single injection of ketamine; after 30 min, the locomotor activity was evaluated in an open field test. Ketamine administration induced an increase in locomotor activity. In the cerebral cortex, hippocampus and striatum, ketamine also induced an increase in reactive oxygen species, lipid peroxidation and nitrite levels, as well a decrease in antioxidant enzyme activity. Pretreatment with blueberry extract or lithium was able to prevent this change. Ketamine increased the AChE and Na+, K+-ATPase activity in brain structures, while the blueberry extract partially prevented these alterations. In addition, our results showed that the neuroprotective effect was not potentiated when lithium and blueberry extract treatment were given together. In conclusion, our findings suggest that blueberry extract has a neuroprotective effect against an experimental model of mania. However, more studies should be performed to evaluate its effects as an adjuvant therapy.


Bipolar disorder Hyperlocomotion Anthocyanins Oxidative stress Acetylcholinesterase Na+, K+-ATPase 



This research was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação de Amparo à Pesquisa do Rio Grande do Sul (FAPERGS). This study was finaced in part by the Coordenação de Aperfeiçoamento de de Nível Superior - Brasil (CAPES) - Finance code 001.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Luiza Spohr
    • 1
  • Mayara Sandrielly Pereira Soares
    • 1
  • Pathise Souto Oliveira
    • 1
  • Bruna da Silveira de Mattos
    • 1
  • Natália Pontes Bona
    • 1
  • Nathalia Stark Pedra
    • 1
  • Fernanda Cardoso Teixeira
    • 1
  • Carlus Augustu Tavares do Couto
    • 1
  • Vitor Clasen Chaves
    • 2
  • Flávio Henrique Reginatto
    • 2
  • Meibel Teixeira Lisboa
    • 3
  • Anderson Schwingel Ribeiro
    • 3
  • Claiton Leoneti Lencina
    • 4
  • Francieli Moro Stefanello
    • 1
  • Roselia Maria Spanevello
    • 1
    Email author
  1. 1.Programa de Pós-Graduação em Bioquímica e Bioprospecção, Centro de Ciências Químicas, Farmacêuticas e de AlimentosUniversidade Federal de PelotasPelotasBrazil
  2. 2.Programa de Pós-Graduação em Biotecnologia e BiociênciasUniversidade Federal de Santa CatarinaFlorianópolisBrazil
  3. 3.Programa de Pós-Graduação em Química, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Laboratório de Metrologia QuímicaUniversidade Federal de PelotasPelotasBrazil
  4. 4.Curso de Farmácia, Centro de Ciências Químicas, Farmacêuticas e de AlimentosUniversidade Federal de PelotasPelotasBrazil

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