1. Lithium modulates the production of peripheral and cerebral cytokines in an animal model of mania induced by dextroamphetamine.
- Author
-
Valvassori SS, Tonin PT, Varela RB, Carvalho AF, Mariot E, Amboni RT, Bianchini G, Andersen ML, and Quevedo J
- Subjects
- Animals, Antimanic Agents therapeutic use, Bipolar Disorder chemically induced, Bipolar Disorder drug therapy, Brain immunology, Central Nervous System Stimulants toxicity, Cytokines cerebrospinal fluid, Cytokines immunology, Dextroamphetamine toxicity, Disease Models, Animal, Frontal Lobe drug effects, Frontal Lobe immunology, Hippocampus drug effects, Hippocampus immunology, Hyperkinesis chemically induced, Hyperkinesis drug therapy, Hyperkinesis immunology, Interleukin-10 cerebrospinal fluid, Interleukin-10 immunology, Interleukin-1beta cerebrospinal fluid, Interleukin-1beta drug effects, Interleukin-1beta immunology, Interleukin-4 cerebrospinal fluid, Interleukin-4 immunology, Interleukin-6 cerebrospinal fluid, Interleukin-6 immunology, Lithium Compounds therapeutic use, Male, Motor Activity immunology, Neostriatum drug effects, Neostriatum immunology, Rats, Rats, Wistar, Tumor Necrosis Factor-alpha cerebrospinal fluid, Tumor Necrosis Factor-alpha drug effects, Tumor Necrosis Factor-alpha immunology, Antimanic Agents pharmacology, Behavior, Animal drug effects, Bipolar Disorder immunology, Brain drug effects, Cytokines drug effects, Lithium Compounds pharmacology, Motor Activity drug effects
- Abstract
Objectives: Several recent studies have suggested that the physiopathology of bipolar disorder (BD) is related to immune system alterations and inflammation. Lithium (Li) is a mood stabilizer that is considered the first-line treatment for this mood disorder. The goal of the present study was to investigate the effects of Li administration on behavior and cytokine levels [interleukin (IL)-1β, IL-4, IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α)] in the periphery and brains of rats subjected to an animal model of mania induced by amphetamine (d-AMPH)., Methods: Male Wistar rats were treated with d-AMPH or saline (Sal) for 14 days; on Day 8 of treatment, the rats were administered Li or Sal for the final seven days. Cytokine (IL-1β, IL-4, IL-6, IL-10, and TNF-α) levels were evaluated in the cerebrospinal fluid (CSF), serum, frontal cortex, striatum, and hippocampus., Results: The present study showed that d-AMPH induced hyperactivity in rats (p < 0.001), and Li treatment reversed this behavioral alteration (p < 0.001). In addition, d-AMPH increased the levels of IL-4, IL-6, IL-10, and TNF-α in the frontal cortex (p < 0.001), striatum (p < 0.001), and serum (p < 0.001), and treatment with Li reversed these cytokine alterations (p < 0.001)., Conclusions: Li modulates peripheral and cerebral cytokine production in an animal model of mania induced by d-AMPH, suggesting that its action on the inflammatory system may contribute to its therapeutic efficacy., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2015
- Full Text
- View/download PDF