N-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related ΔFosB alterations

dc.contributor.authorMorais-Silva, Gessynger [UNESP]
dc.contributor.authorAlves, Gabrielle Cunha [UNESP]
dc.contributor.authorMarin, Marcelo T. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2018-12-11T16:43:22Z
dc.date.available2018-12-11T16:43:22Z
dc.date.issued2016-11-01
dc.description.abstractEthanol 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.en
dc.description.affiliationLaboratory of Pharmacology School of Pharmaceutical Sciences Univ Estadual Paulista – UNESP
dc.description.affiliationJoint Graduate Programme in Physiological Sciences UFSCar/UNESP
dc.description.affiliationUnespLaboratory of Pharmacology School of Pharmaceutical Sciences Univ Estadual Paulista – UNESP
dc.description.affiliationUnespJoint Graduate Programme in Physiological Sciences UFSCar/UNESP
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdFAPESP: 2014/02371-9
dc.format.extent135-142
dc.identifierhttp://dx.doi.org/10.1016/j.neuropharm.2016.07.009
dc.identifier.citationNeuropharmacology, v. 110, p. 135-142.
dc.identifier.doi10.1016/j.neuropharm.2016.07.009
dc.identifier.issn1873-7064
dc.identifier.issn0028-3908
dc.identifier.scopus2-s2.0-84979783823
dc.identifier.urihttp://hdl.handle.net/11449/168853
dc.language.isoeng
dc.relation.ispartofNeuropharmacology
dc.relation.ispartofsjr2,043
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectAlcohol addiction
dc.subjectGlutamate
dc.subjectN-acetylcysteine
dc.subjectNucleus accumbens
dc.subjectPrefrontal cortex
dc.subjectxCT antiporter
dc.titleN-acetylcysteine treatment blocks the development of ethanol-induced behavioural sensitization and related ΔFosB alterationsen
dc.typeArtigo
unesp.author.orcid0000-0002-0522-2839 0000-0002-0522-2839[3]

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