Methamphetamine‐Induced Early Increase of IL‐6 and TNF‐α 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.

Effects of chronic treatment with methylphenidate on oxidative stress and inflammation in hippocampus of adult rats

“…We observed that high doses of MPH can induce neuroinflammation, as is evident by increased IL-1β (ng/ml) and TNF-α (ng/ml) levels. Similar to our findings, Gonçalves et al, reported methamphetamine induced rise in the expression of inflammatory cytokines like TNF-α, IL-1-β and IL-6 in the rat spinal cord and brain [11]. Many previous studies demonstrated that neurodegenerative effects of MPH and methamphetamine like compounds mediated by inflammatory pathway and TNF-α and IL-1β play significant role in this process.…”

Psychostimulant Abuse and Neuroinflammation: Emerging Evidence of Their Interconnection

“…A study using RT-PCR showed increased mRNA expression of microglial-produced pro-inflammatory cytokines IL-6 and TNF-a in the striatum and hippocampus of mice following acute high dose (30 mg/kg) methamphetamine exposure (Goncalves et al 2008). Microglial activation in response to psychostimulants has also been demonstrated by a recent series of experiments by Wisor et al (2011) at much lower doses of methamphetamine.…”

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

“…In the brain, acute cocaine results in increased IL-1β mRNA in the NAc and cortex (Cearley et al, 2011), while methamphetamine leads to increased IL-6 and TNFα in hippocampus and frontal cortex (Gonçalves et al, 2008). Similarly, acute injections of cocaine results in elevated IL-1β mRNA in the VTA, an effect that is blocked with (+)-naloxone treatment (Northcutt et al, 2015).…”