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Lithium modulates the production of peripheral and cerebral cytokines in an animal model of mania induced by dextroamphetamine.
Bipolar Disord 2015; 17(5):507-17BD

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.

Authors+Show Affiliations

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.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.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.Department of Psychiatry and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil.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.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.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.Departamento de Psicologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25929806

Citation

Valvassori, Samira S., et al. "Lithium Modulates the Production of Peripheral and Cerebral Cytokines in an Animal Model of Mania Induced By Dextroamphetamine." Bipolar Disorders, vol. 17, no. 5, 2015, pp. 507-17.
Valvassori SS, Tonin PT, Varela RB, et al. Lithium modulates the production of peripheral and cerebral cytokines in an animal model of mania induced by dextroamphetamine. Bipolar Disord. 2015;17(5):507-17.
Valvassori, S. S., Tonin, P. T., Varela, R. B., Carvalho, A. F., Mariot, E., Amboni, R. T., ... Quevedo, J. (2015). Lithium modulates the production of peripheral and cerebral cytokines in an animal model of mania induced by dextroamphetamine. Bipolar Disorders, 17(5), pp. 507-17. doi:10.1111/bdi.12299.
Valvassori SS, et al. Lithium Modulates the Production of Peripheral and Cerebral Cytokines in an Animal Model of Mania Induced By Dextroamphetamine. Bipolar Disord. 2015;17(5):507-17. PubMed PMID: 25929806.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lithium modulates the production of peripheral and cerebral cytokines in an animal model of mania induced by dextroamphetamine. AU - Valvassori,Samira S, AU - Tonin,Paula T, AU - Varela,Roger B, AU - Carvalho,André F, AU - Mariot,Edemilson, AU - Amboni,Rafaela T, AU - Bianchini,Guilherme, AU - Andersen,Monica L, AU - Quevedo,João, Y1 - 2015/04/30/ PY - 2014/10/17/received PY - 2015/01/09/accepted PY - 2015/5/2/entrez PY - 2015/5/2/pubmed PY - 2016/3/10/medline KW - amphetamine KW - bipolar disorder KW - cytokines KW - lithium KW - mania SP - 507 EP - 17 JF - Bipolar disorders JO - Bipolar Disord VL - 17 IS - 5 N2 - 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. SN - 1399-5618 UR - https://www.unboundmedicine.com/medline/citation/25929806/Lithium_modulates_the_production_of_peripheral_and_cerebral_cytokines_in_an_animal_model_of_mania_induced_by_dextroamphetamine_ L2 - https://doi.org/10.1111/bdi.12299 DB - PRIME DP - Unbound Medicine ER -