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Effects of N-acetylcysteine on amphetamine-induced sensitization in mice
OBJECTIVE: N-acetylcysteine (NAC) is beneficial in psychiatric conditions, including schizophrenia. Patients with schizophrenia exhibit mesolimbic dopamine hyperfunction consequent to an endogenous sensitization process. This sensitization can be modeled in rodents by repeated exposure to psychostim...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Associação Brasileira de Psiquiatria
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900759/ https://www.ncbi.nlm.nih.gov/pubmed/29236922 http://dx.doi.org/10.1590/1516-4446-2017-2337 |
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author | Herrmann, Ana P. Andrejew, Roberta Benvenutti, Radharani Gama, Clarissa S. Elisabetsky, Elaine |
author_facet | Herrmann, Ana P. Andrejew, Roberta Benvenutti, Radharani Gama, Clarissa S. Elisabetsky, Elaine |
author_sort | Herrmann, Ana P. |
collection | PubMed |
description | OBJECTIVE: N-acetylcysteine (NAC) is beneficial in psychiatric conditions, including schizophrenia. Patients with schizophrenia exhibit mesolimbic dopamine hyperfunction consequent to an endogenous sensitization process. This sensitization can be modeled in rodents by repeated exposure to psychostimulants, provoking an enduring amplified response at subsequent exposure. The aim of this study was to investigate the effects of NAC on amphetamine sensitization in mice. METHODS: D-amphetamine was administered to C57BL/6 mice three times a week for 3 weeks; the dose was increased weekly from 1 to 3 mg/kg. NAC (60 mg/kg) or saline was administered intraperitoneally before saline or amphetamine during the second and third weeks. After a 4-week washout period, latent inhibition (LI) and the locomotor response to amphetamine 2 mg/kg were assessed. RESULTS: Sensitization disrupted LI and amplified the locomotor response; NAC disrupted LI in control mice. In sensitized animals, NAC attenuated the enhanced locomotion but failed to prevent LI disruption. CONCLUSION: NAC warrants consideration as a candidate for early intervention in ultra-high risk subjects due to its safety profile and the relevance of its mechanism of action. Supplementing this proposition, we report that NAC attenuates sensitization-induced locomotor enhancement in mice. The finding that NAC disrupted LI incites a cautionary note and requires clarification. |
format | Online Article Text |
id | pubmed-6900759 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Associação Brasileira de Psiquiatria |
record_format | MEDLINE/PubMed |
spelling | pubmed-69007592019-12-30 Effects of N-acetylcysteine on amphetamine-induced sensitization in mice Herrmann, Ana P. Andrejew, Roberta Benvenutti, Radharani Gama, Clarissa S. Elisabetsky, Elaine Braz J Psychiatry Original Article OBJECTIVE: N-acetylcysteine (NAC) is beneficial in psychiatric conditions, including schizophrenia. Patients with schizophrenia exhibit mesolimbic dopamine hyperfunction consequent to an endogenous sensitization process. This sensitization can be modeled in rodents by repeated exposure to psychostimulants, provoking an enduring amplified response at subsequent exposure. The aim of this study was to investigate the effects of NAC on amphetamine sensitization in mice. METHODS: D-amphetamine was administered to C57BL/6 mice three times a week for 3 weeks; the dose was increased weekly from 1 to 3 mg/kg. NAC (60 mg/kg) or saline was administered intraperitoneally before saline or amphetamine during the second and third weeks. After a 4-week washout period, latent inhibition (LI) and the locomotor response to amphetamine 2 mg/kg were assessed. RESULTS: Sensitization disrupted LI and amplified the locomotor response; NAC disrupted LI in control mice. In sensitized animals, NAC attenuated the enhanced locomotion but failed to prevent LI disruption. CONCLUSION: NAC warrants consideration as a candidate for early intervention in ultra-high risk subjects due to its safety profile and the relevance of its mechanism of action. Supplementing this proposition, we report that NAC attenuates sensitization-induced locomotor enhancement in mice. The finding that NAC disrupted LI incites a cautionary note and requires clarification. Associação Brasileira de Psiquiatria 2017-12-11 /pmc/articles/PMC6900759/ /pubmed/29236922 http://dx.doi.org/10.1590/1516-4446-2017-2337 Text en http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Herrmann, Ana P. Andrejew, Roberta Benvenutti, Radharani Gama, Clarissa S. Elisabetsky, Elaine Effects of N-acetylcysteine on amphetamine-induced sensitization in mice |
title | Effects of N-acetylcysteine on amphetamine-induced sensitization in mice |
title_full | Effects of N-acetylcysteine on amphetamine-induced sensitization in mice |
title_fullStr | Effects of N-acetylcysteine on amphetamine-induced sensitization in mice |
title_full_unstemmed | Effects of N-acetylcysteine on amphetamine-induced sensitization in mice |
title_short | Effects of N-acetylcysteine on amphetamine-induced sensitization in mice |
title_sort | effects of n-acetylcysteine on amphetamine-induced sensitization in mice |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900759/ https://www.ncbi.nlm.nih.gov/pubmed/29236922 http://dx.doi.org/10.1590/1516-4446-2017-2337 |
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