Lithium modulates the production of peripheral and cerebral cytokines in an animal model of mania induced by dextroamphetamine.
OBJECTIVE
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.
Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Samira S
SS
Valvassori
Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Paula T
PT
Tonin
Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Roger B
RB
Varela
Department of Psychiatry and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil.
André F
AF
Carvalho
Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Edemilson
E
Mariot
Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Rafaela T
RT
Amboni
Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Guilherme
G
Bianchini
Departamento de Psicologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Monica L
ML
Andersen
Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.|Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, University of Texas Medical School at Houston, Houston, TX, USA.
João
J
Quevedo
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D001714:Bipolar Disorder / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology*; D001921:Brain / Q000187:drug effects* / Q000276:immunology; D000697:Central Nervous System Stimulants / Q000633:toxicity; D016207:Cytokines / Q000134:cerebrospinal fluid / Q000187:drug effects* / Q000276:immunology; D003913:Dextroamphetamine / Q000633:toxicity; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000187:drug effects / Q000276:immunology; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D016753:Interleukin-10 / Q000134:cerebrospinal fluid / Q000276:immunology; D053583:Interleukin-1beta / Q000134:cerebrospinal fluid / Q000187:drug effects / Q000276:immunology; D015847:Interleukin-4 / Q000134:cerebrospinal fluid / Q000276:immunology; D015850:Interleukin-6 / Q000134:cerebrospinal fluid / Q000276:immunology; D018020:Lithium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000276:immunology; D017072:Neostriatum / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid / Q000187:drug effects / Q000276:immunology
D018692:Antimanic Agents; D000697:Central Nervous System Stimulants; D016207:Cytokines; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D015850:Interleukin-6; D018020:Lithium Compounds; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D003913:Dextroamphetamine
amphetamine; bipolar disorder; cytokines; lithium; mania