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A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
Published on: January 22, 2016
Modafinil abrogates methamphetamine-induced neuroinflammation and apoptotic effects in the mouse striatum
Mariana Raineri1, Betina Gonzalez, Belen Goitia
1Instituto de Investigaciones Farmacológicas (Universidad de Buenos Aires - Consejo Nacional de Investigaciones Científicas y Técnicas), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
Abstract:
Methamphetamine is a drug of abuse that can cause neurotoxic damage in humans and animals. Modafinil, a wake-promoting compound approved for the treatment of sleeping disorders, is being prescribed off label for the treatment of methamphetamine dependence. The aim of the present study was to investigate if modafinil could counteract methamphetamine-induced neuroinflammatory processes, which occur in conjunction with degeneration of dopaminergic terminals in the mouse striatum. We evaluated the effect of a toxic methamphetamine binge in female C57BL/6 mice (4 × 5 mg/kg, i.p., 2 h apart) and modafinil co-administration (2 × 90 mg/kg, i.p., 1 h before the first and fourth methamphetamine injections) on glial cells (microglia and astroglia). We also evaluated the striatal expression of the pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins, which are known to mediate methamphetamine-induced apoptotic effects. Modafinil by itself did not cause reactive gliosis and counteracted methamphetamine-induced microglial and astroglial activation. Modafinil also counteracted the decrease in tyrosine hydroxylase and dopamine transporter levels and prevented methamphetamine-induced increases in the pro-apoptotic BAX and decreases in the anti-apoptotic Bcl-2 protein expression. Our results indicate that modafinil can interfere with methamphetamine actions and provide protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum.
Insights
Modafinil protects against methamphetamine-induced neurotoxicity by reducing neuroinflammation and cell death in the mouse striatum. This study shows modafinil counteracts methamphetamine
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Methamphetamine abuse causes significant neurotoxic damage.
- Modafinil, used for sleep disorders, is explored for treating methamphetamine dependence.
- Neuroinflammation and dopaminergic terminal degeneration are key consequences of methamphetamine toxicity.
Purpose of the Study:
- To investigate modafinil's potential to counteract methamphetamine-induced neuroinflammation.
- To assess modafinil's effect on glial cell activation (microglia and astroglia) in the mouse striatum.
- To evaluate modafinil's impact on apoptotic markers (BAX and Bcl-2) and dopaminergic terminal integrity.
Main Methods:
- Female C57BL/6 mice were administered a toxic methamphetamine binge.
- Modafinil was co-administered to assess its protective effects.
- Glial cell activation, tyrosine hydroxylase, dopamine transporter, and apoptotic protein expression were analyzed in the striatum.
Main Results:
- Modafinil alone did not induce reactive gliosis.
- Modafinil counteracted methamphetamine-induced microglial and astroglial activation.
- Modafinil prevented decreases in tyrosine hydroxylase and dopamine transporter levels.
- Modafinil normalized the expression of pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins.
Conclusions:
- Modafinil interferes with methamphetamine's neurotoxic actions.
- Modafinil offers protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum.
- These findings support modafinil's potential therapeutic role in methamphetamine dependence.
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