N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related ΔFosB alterations
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.neuropharm.2016.07.009 http://hdl.handle.net/11449/168853 |
Resumo: | Ethanol addiction is a serious public health problem that still needs more effective pharmacological treatment. A key factor in the development and maintenance of this disease is the advent of neuroadaptations in the mesocorticolimbic brain pathway upon chronic ethanol abuse. In general, these neuroadaptations are maladaptive and affect numerous neurotransmitter systems and intracellular molecules. One of these molecules is ΔFosB, a transcription factor that is altered after chronic drug use. Behavioural sensitization is a useful model for the study of the neuroadaptations related to addiction. Recent works have shown a role for the imbalance of glutamatergic neurotransmission in the symptoms found in addicted people. In this sense, the treatment with N-acetylcysteine, a L-cysteine prodrug that acts by restoring extrasynaptic concentrations of glutamate through the activation of cystine-glutamate antiporter, has shown promising results in the treatment of addiction. Thus, an animal model of behavioural sensitization was used to evaluate the effects of N-acetylcysteine treatment in the behavioural and molecular alterations induced by chronic ethanol administration. Swiss mice were subject to 13 days of daily ethanol administration to induce behavioural sensitization. Two hours before each ethanol administration and locomotor activity evaluation, the animals received intraperitoneally N-acetylcysteine injections. Immediately after the last test session, their brains were removed for ΔFosB and cystine-glutamate antiporter quantification. It was found that N-acetylcysteine treatment blocked ethanol-induced behavioural sensitization, the increase of ΔFosB content in the prefrontal cortex, and its reduction in the nucleus accumbens. The results suggest a possible use of N-acetylcysteine in ethanol-related disorders. |
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N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related ΔFosB alterationsAlcohol addictionGlutamateN-acetylcysteineNucleus accumbensPrefrontal cortexxCT antiporterEthanol addiction is a serious public health problem that still needs more effective pharmacological treatment. A key factor in the development and maintenance of this disease is the advent of neuroadaptations in the mesocorticolimbic brain pathway upon chronic ethanol abuse. In general, these neuroadaptations are maladaptive and affect numerous neurotransmitter systems and intracellular molecules. One of these molecules is ΔFosB, a transcription factor that is altered after chronic drug use. Behavioural sensitization is a useful model for the study of the neuroadaptations related to addiction. Recent works have shown a role for the imbalance of glutamatergic neurotransmission in the symptoms found in addicted people. In this sense, the treatment with N-acetylcysteine, a L-cysteine prodrug that acts by restoring extrasynaptic concentrations of glutamate through the activation of cystine-glutamate antiporter, has shown promising results in the treatment of addiction. Thus, an animal model of behavioural sensitization was used to evaluate the effects of N-acetylcysteine treatment in the behavioural and molecular alterations induced by chronic ethanol administration. Swiss mice were subject to 13 days of daily ethanol administration to induce behavioural sensitization. Two hours before each ethanol administration and locomotor activity evaluation, the animals received intraperitoneally N-acetylcysteine injections. Immediately after the last test session, their brains were removed for ΔFosB and cystine-glutamate antiporter quantification. It was found that N-acetylcysteine treatment blocked ethanol-induced behavioural sensitization, the increase of ΔFosB content in the prefrontal cortex, and its reduction in the nucleus accumbens. The results suggest a possible use of N-acetylcysteine in ethanol-related disorders.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Laboratory of Pharmacology School of Pharmaceutical Sciences Univ Estadual Paulista – UNESPJoint Graduate Programme in Physiological Sciences UFSCar/UNESPLaboratory of Pharmacology School of Pharmaceutical Sciences Univ Estadual Paulista – UNESPJoint Graduate Programme in Physiological Sciences UFSCar/UNESPFAPESP: 2014/02371-9Universidade Estadual Paulista (Unesp)Morais-Silva, Gessynger [UNESP]Alves, Gabrielle Cunha [UNESP]Marin, Marcelo T. [UNESP]2018-12-11T16:43:22Z2018-12-11T16:43:22Z2016-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article135-142http://dx.doi.org/10.1016/j.neuropharm.2016.07.009Neuropharmacology, v. 110, p. 135-142.1873-70640028-3908http://hdl.handle.net/11449/16885310.1016/j.neuropharm.2016.07.0092-s2.0-84979783823Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengNeuropharmacology2,043info:eu-repo/semantics/openAccess2021-10-23T09:49:03Zoai:repositorio.unesp.br:11449/168853Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T09:49:03Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related ΔFosB alterations |
title |
N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related ΔFosB alterations |
spellingShingle |
N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related ΔFosB alterations Morais-Silva, Gessynger [UNESP] Alcohol addiction Glutamate N-acetylcysteine Nucleus accumbens Prefrontal cortex xCT antiporter |
title_short |
N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related ΔFosB alterations |
title_full |
N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related ΔFosB alterations |
title_fullStr |
N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related ΔFosB alterations |
title_full_unstemmed |
N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related ΔFosB alterations |
title_sort |
N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related ΔFosB alterations |
author |
Morais-Silva, Gessynger [UNESP] |
author_facet |
Morais-Silva, Gessynger [UNESP] Alves, Gabrielle Cunha [UNESP] Marin, Marcelo T. [UNESP] |
author_role |
author |
author2 |
Alves, Gabrielle Cunha [UNESP] Marin, Marcelo T. [UNESP] |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Morais-Silva, Gessynger [UNESP] Alves, Gabrielle Cunha [UNESP] Marin, Marcelo T. [UNESP] |
dc.subject.por.fl_str_mv |
Alcohol addiction Glutamate N-acetylcysteine Nucleus accumbens Prefrontal cortex xCT antiporter |
topic |
Alcohol addiction Glutamate N-acetylcysteine Nucleus accumbens Prefrontal cortex xCT antiporter |
description |
Ethanol addiction is a serious public health problem that still needs more effective pharmacological treatment. A key factor in the development and maintenance of this disease is the advent of neuroadaptations in the mesocorticolimbic brain pathway upon chronic ethanol abuse. In general, these neuroadaptations are maladaptive and affect numerous neurotransmitter systems and intracellular molecules. One of these molecules is ΔFosB, a transcription factor that is altered after chronic drug use. Behavioural sensitization is a useful model for the study of the neuroadaptations related to addiction. Recent works have shown a role for the imbalance of glutamatergic neurotransmission in the symptoms found in addicted people. In this sense, the treatment with N-acetylcysteine, a L-cysteine prodrug that acts by restoring extrasynaptic concentrations of glutamate through the activation of cystine-glutamate antiporter, has shown promising results in the treatment of addiction. Thus, an animal model of behavioural sensitization was used to evaluate the effects of N-acetylcysteine treatment in the behavioural and molecular alterations induced by chronic ethanol administration. Swiss mice were subject to 13 days of daily ethanol administration to induce behavioural sensitization. Two hours before each ethanol administration and locomotor activity evaluation, the animals received intraperitoneally N-acetylcysteine injections. Immediately after the last test session, their brains were removed for ΔFosB and cystine-glutamate antiporter quantification. It was found that N-acetylcysteine treatment blocked ethanol-induced behavioural sensitization, the increase of ΔFosB content in the prefrontal cortex, and its reduction in the nucleus accumbens. The results suggest a possible use of N-acetylcysteine in ethanol-related disorders. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-11-01 2018-12-11T16:43:22Z 2018-12-11T16:43:22Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.neuropharm.2016.07.009 Neuropharmacology, v. 110, p. 135-142. 1873-7064 0028-3908 http://hdl.handle.net/11449/168853 10.1016/j.neuropharm.2016.07.009 2-s2.0-84979783823 |
url |
http://dx.doi.org/10.1016/j.neuropharm.2016.07.009 http://hdl.handle.net/11449/168853 |
identifier_str_mv |
Neuropharmacology, v. 110, p. 135-142. 1873-7064 0028-3908 10.1016/j.neuropharm.2016.07.009 2-s2.0-84979783823 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Neuropharmacology 2,043 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
135-142 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1797790253668368384 |