title: Methamphetamine-induced early increase of IL-6 and TNF-alpha mRNA expression in the mouse brain.
abstract: The mechanisms by which methamphetamine (METH) causes neurotoxicity are not well understood. Recent studies have suggested that METH-induced neuropathology may result from a multicellular response in which glial cells play a prominent role, and so it is plausible to suggest that cytokines may participate in the toxic effects of METH. Therefore, in the present work we evaluated the effect of an acute administration of METH (30 mg/kg in a single intraperitoneal injection) on the interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha mRNA expression levels in the hippocampus, frontal cortex, and striatum of mice. We observed that METH did not induce changes in the IL-1beta mRNA expression levels in both hippocampus and striatum, with immeasurable levels in the frontal cortex. Regarding IL-6, METH induced an increase in the expression levels of this cytokine in the hippocampus and striatum, 1 h and 30 min post injection, respectively. In the frontal cortex, the increase in IL-6 mRNA levels was more significant and remained high even after 2 h. Moreover, the expression levels of TNF-alpha were increased in both hippocampus and frontal cortex 30 min post METH administration, with immeasurable levels in the striatum. We conclude that the pro-inflammatory cytokines IL-6 and TNF-alpha rapidly increase after METH administration, providing a new insight for understanding the effect of this drug of abuse in the brain.
authors.affiliation: Institute of Pharmacology and Therapeutics, and Biomedical Institute for Research in Light and Image, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Gonçalves
authors.forename: Tânia
authors.initials: T
authors.lastname: Martins
authors.forename: Raquel
authors.initials: R
authors.lastname: Ferreira
authors.forename: Nuno
authors.initials: N
authors.lastname: Milhazes
authors.forename: Fernanda
authors.initials: F
authors.lastname: Borges
authors.forename: Carlos Fontes
authors.initials: CF
authors.lastname: Ribeiro
authors.forename: João O
authors.initials: JO
authors.lastname: Malva
authors.forename: Tice R
authors.initials: TR
authors.lastname: Macedo
authors.forename: Ana P
authors.initials: AP
authors.lastname: Silva
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D008694:Methamphetamine