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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.

Registro:

Documento: Artículo
Título:Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum
Autor:Raineri, M.; Gonzalez, B.; Goitia, B.; Garcia-Rill, E.; Krasnova, I.N.; Cadet, J.L.; Urbano, F.J.; Bisagno, V.
Filiación:Instituto de Investigaciones Farmacológicas, Universidad de Buenos Aires - Consejo Nacional de Investigaciones Cientificas y Tecnicas, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Laboratorio de Fisiología y Biología Molecular, Instituto de Fisiología, Biología Molecular y Neurociencias, Univ. de Buenos Aires - Consejo Nacional de Inves. Cientificas y Tecnicas, Ciudad Autonoma de Buenos, Buenos Aires, Argentina
Molecular Neuropsychiatry Research Branch, NIH/NIDA Intramural Research Program, Baltimore, MD, United States
Center for Translational Neuroscience, Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States
Palabras clave: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
Año:2012
Volumen:7
Número:10
DOI: http://dx.doi.org/10.1371/journal.pone.0046599
Título revista:PLoS ONE
Título revista abreviado:PLoS ONE
ISSN:19326203
CAS:methamphetamine, 28297-73-6, 51-57-0, 537-46-2, 7632-10-2; modafinil, 68693-11-8; protein bcl 2, 219306-68-0; tyrosine 3 monooxygenase, 9036-22-0; Benzhydryl Compounds; Dopamine Plasma Membrane Transport Proteins; Glial Fibrillary Acidic Protein; Methamphetamine, 537-46-2; Tyrosine 3-Monooxygenase, 1.14.16.2; modafinil, 68693-11-8
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v7_n10_p_Raineri

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Citas:

---------- APA ----------
Raineri, M., Gonzalez, B., Goitia, B., Garcia-Rill, E., Krasnova, I.N., Cadet, J.L., Urbano, F.J.,..., Bisagno, V. (2012) . Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum. PLoS ONE, 7(10).
http://dx.doi.org/10.1371/journal.pone.0046599
---------- CHICAGO ----------
Raineri, M., Gonzalez, B., Goitia, B., Garcia-Rill, E., Krasnova, I.N., Cadet, J.L., et al. "Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum" . PLoS ONE 7, no. 10 (2012).
http://dx.doi.org/10.1371/journal.pone.0046599
---------- MLA ----------
Raineri, M., Gonzalez, B., Goitia, B., Garcia-Rill, E., Krasnova, I.N., Cadet, J.L., et al. "Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum" . PLoS ONE, vol. 7, no. 10, 2012.
http://dx.doi.org/10.1371/journal.pone.0046599
---------- VANCOUVER ----------
Raineri, M., Gonzalez, B., Goitia, B., Garcia-Rill, E., Krasnova, I.N., Cadet, J.L., et al. Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum. PLoS ONE. 2012;7(10).
http://dx.doi.org/10.1371/journal.pone.0046599