Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum
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 investi...
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2012
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v7_n10_p_Raineri http://hdl.handle.net/20.500.12110/paper_19326203_v7_n10_p_Raineri |
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paper:paper_19326203_v7_n10_p_Raineri2023-06-08T16:31:00Z Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum dopamine transporter methamphetamine modafinil protein Bax protein bcl 2 tyrosine 3 monooxygenase animal cell animal experiment animal model animal tissue apoptosis article C57BL 6 mouse cell death corpus striatum dopaminergic nerve cell female gliosis macroglia microglia mouse nerve cell degeneration nervous system inflammation neuroprotection nonhuman protein expression Animals Apoptosis Benzhydryl Compounds Corpus Striatum Dopamine Plasma Membrane Transport Proteins Female Fever Glial Fibrillary Acidic Protein Immunohistochemistry Inflammation Methamphetamine Mice Mice, Inbred C57BL Tyrosine 3-Monooxygenase Animalia Mus 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. 2012 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v7_n10_p_Raineri http://hdl.handle.net/20.500.12110/paper_19326203_v7_n10_p_Raineri |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
dopamine transporter methamphetamine modafinil protein Bax protein bcl 2 tyrosine 3 monooxygenase animal cell animal experiment animal model animal tissue apoptosis article C57BL 6 mouse cell death corpus striatum dopaminergic nerve cell female gliosis macroglia microglia mouse nerve cell degeneration nervous system inflammation neuroprotection nonhuman protein expression Animals Apoptosis Benzhydryl Compounds Corpus Striatum Dopamine Plasma Membrane Transport Proteins Female Fever Glial Fibrillary Acidic Protein Immunohistochemistry Inflammation Methamphetamine Mice Mice, Inbred C57BL Tyrosine 3-Monooxygenase Animalia Mus |
| spellingShingle |
dopamine transporter methamphetamine modafinil protein Bax protein bcl 2 tyrosine 3 monooxygenase animal cell animal experiment animal model animal tissue apoptosis article C57BL 6 mouse cell death corpus striatum dopaminergic nerve cell female gliosis macroglia microglia mouse nerve cell degeneration nervous system inflammation neuroprotection nonhuman protein expression Animals Apoptosis Benzhydryl Compounds Corpus Striatum Dopamine Plasma Membrane Transport Proteins Female Fever Glial Fibrillary Acidic Protein Immunohistochemistry Inflammation Methamphetamine Mice Mice, Inbred C57BL Tyrosine 3-Monooxygenase Animalia Mus Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum |
| topic_facet |
dopamine transporter methamphetamine modafinil protein Bax protein bcl 2 tyrosine 3 monooxygenase animal cell animal experiment animal model animal tissue apoptosis article C57BL 6 mouse cell death corpus striatum dopaminergic nerve cell female gliosis macroglia microglia mouse nerve cell degeneration nervous system inflammation neuroprotection nonhuman protein expression Animals Apoptosis Benzhydryl Compounds Corpus Striatum Dopamine Plasma Membrane Transport Proteins Female Fever Glial Fibrillary Acidic Protein Immunohistochemistry Inflammation Methamphetamine Mice Mice, Inbred C57BL Tyrosine 3-Monooxygenase Animalia Mus |
| description |
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. |
| title |
Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum |
| title_short |
Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum |
| title_full |
Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum |
| title_fullStr |
Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum |
| title_full_unstemmed |
Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum |
| title_sort |
modafinil abrogates methamphetamine-induced neuroinflammation and apoptotic effects in the mouse striatum |
| publishDate |
2012 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v7_n10_p_Raineri http://hdl.handle.net/20.500.12110/paper_19326203_v7_n10_p_Raineri |
| _version_ |
1768543441180950528 |