Effects of lithium on inflammatory and neurotrophic factors after an immune challenge in a lisdexamfetamine animal model of mania

Braz J Psychiatry. 2019 Mar 7;41(5):419-427. doi: 10.1590/1516-4446-2017-0001. eCollection 2019.

Abstract

Objective: To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors.

Methods: Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals' blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1β, IL-10, and inducible nitric oxide synthase [iNOS]) were measured.

Results: LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation.

Conclusion: Although Li prevented an LPS-induced increase in serum iNOS levels, its potential anti-inflammatory effects in this animal model of mania were conflicting.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Bipolar Disorder / chemically induced
  • Bipolar Disorder / immunology*
  • Bipolar Disorder / physiopathology
  • Brain-Derived Neurotrophic Factor / blood
  • Cytokines / blood
  • Disease Models, Animal*
  • Enzyme-Linked Immunosorbent Assay
  • Lipopolysaccharides / pharmacology
  • Lisdexamfetamine Dimesylate*
  • Lithium / pharmacology*
  • Locomotion / drug effects
  • Male
  • Nerve Growth Factors / drug effects*
  • Nitric Oxide Synthase Type II / blood
  • Rats, Wistar
  • Reproducibility of Results
  • Time Factors
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Cytokines
  • Lipopolysaccharides
  • Nerve Growth Factors
  • Lithium
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Lisdexamfetamine Dimesylate