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Milnacipran Remediates Impulsive Deficits in Rats with Lesions of the Ventromedial Prefrontal Cortex
BACKGROUND: Deficits in impulse control are often observed in psychiatric disorders in which abnormalities of the prefrontal cortex are observed, including attention-deficit/hyperactivity disorder and bipolar disorder. We recently found that milnacipran, a serotonin/noradrenaline reuptake inhibitor,...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376543/ https://www.ncbi.nlm.nih.gov/pubmed/25522418 http://dx.doi.org/10.1093/ijnp/pyu083 |
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author | Tsutsui-Kimura, Iku Yoshida, Takayuki Ohmura, Yu Izumi, Takeshi Yoshioka, Mitsuhiro |
author_facet | Tsutsui-Kimura, Iku Yoshida, Takayuki Ohmura, Yu Izumi, Takeshi Yoshioka, Mitsuhiro |
author_sort | Tsutsui-Kimura, Iku |
collection | PubMed |
description | BACKGROUND: Deficits in impulse control are often observed in psychiatric disorders in which abnormalities of the prefrontal cortex are observed, including attention-deficit/hyperactivity disorder and bipolar disorder. We recently found that milnacipran, a serotonin/noradrenaline reuptake inhibitor, could suppress impulsive action in normal rats. However, whether milnacipran could suppress elevated impulsive action in rats with lesions of the ventromedial prefrontal cortex, which is functionally comparable with the human prefrontal cortex, remains unknown. METHODS: Selective lesions of the ventromedial prefrontal cortex were made using quinolinic acid in rats previously trained on a 3-choice serial reaction time task. Sham rats received phosphate buffered saline. Following a period of recovery, milnacipran (0 or 10mg/kg/d × 14 days) was orally administered 60 minutes prior to testing on the 3-choice task. After 7 days of drug cessation, Western blotting, immunohistochemistry, electrophysiological analysis, and morphological analysis were conducted. RESULTS: Lesions of the ventromedial prefrontal cortex induced impulsive deficits, and repeated milnacipran ameliorated the impulsive deficit both during the dosing period and after the cessation of the drug. Repeated milnacipran remediated the protein levels of mature brain-derived neurotrophic factor and postsynaptic density-95, dendritic spine density, and excitatory currents in the few surviving neurons in the ventromedial prefrontal cortex of ventromedial prefrontal cortex-lesioned rats. CONCLUSIONS: The findings of this study suggest that milnacipran treatment could be a novel strategy for the treatment of psychiatric disorders that are associated with a lack of impulse control. |
format | Online Article Text |
id | pubmed-4376543 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-43765432015-09-01 Milnacipran Remediates Impulsive Deficits in Rats with Lesions of the Ventromedial Prefrontal Cortex Tsutsui-Kimura, Iku Yoshida, Takayuki Ohmura, Yu Izumi, Takeshi Yoshioka, Mitsuhiro Int J Neuropsychopharmacol Research Article BACKGROUND: Deficits in impulse control are often observed in psychiatric disorders in which abnormalities of the prefrontal cortex are observed, including attention-deficit/hyperactivity disorder and bipolar disorder. We recently found that milnacipran, a serotonin/noradrenaline reuptake inhibitor, could suppress impulsive action in normal rats. However, whether milnacipran could suppress elevated impulsive action in rats with lesions of the ventromedial prefrontal cortex, which is functionally comparable with the human prefrontal cortex, remains unknown. METHODS: Selective lesions of the ventromedial prefrontal cortex were made using quinolinic acid in rats previously trained on a 3-choice serial reaction time task. Sham rats received phosphate buffered saline. Following a period of recovery, milnacipran (0 or 10mg/kg/d × 14 days) was orally administered 60 minutes prior to testing on the 3-choice task. After 7 days of drug cessation, Western blotting, immunohistochemistry, electrophysiological analysis, and morphological analysis were conducted. RESULTS: Lesions of the ventromedial prefrontal cortex induced impulsive deficits, and repeated milnacipran ameliorated the impulsive deficit both during the dosing period and after the cessation of the drug. Repeated milnacipran remediated the protein levels of mature brain-derived neurotrophic factor and postsynaptic density-95, dendritic spine density, and excitatory currents in the few surviving neurons in the ventromedial prefrontal cortex of ventromedial prefrontal cortex-lesioned rats. CONCLUSIONS: The findings of this study suggest that milnacipran treatment could be a novel strategy for the treatment of psychiatric disorders that are associated with a lack of impulse control. Oxford University Press 2015-01-28 /pmc/articles/PMC4376543/ /pubmed/25522418 http://dx.doi.org/10.1093/ijnp/pyu083 Text en © The Author 2015. Published by Oxford University Press on behalf of CINP. 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 (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Research Article Tsutsui-Kimura, Iku Yoshida, Takayuki Ohmura, Yu Izumi, Takeshi Yoshioka, Mitsuhiro Milnacipran Remediates Impulsive Deficits in Rats with Lesions of the Ventromedial Prefrontal Cortex |
title | Milnacipran Remediates Impulsive Deficits in Rats with Lesions of the Ventromedial Prefrontal Cortex |
title_full | Milnacipran Remediates Impulsive Deficits in Rats with Lesions of the Ventromedial Prefrontal Cortex |
title_fullStr | Milnacipran Remediates Impulsive Deficits in Rats with Lesions of the Ventromedial Prefrontal Cortex |
title_full_unstemmed | Milnacipran Remediates Impulsive Deficits in Rats with Lesions of the Ventromedial Prefrontal Cortex |
title_short | Milnacipran Remediates Impulsive Deficits in Rats with Lesions of the Ventromedial Prefrontal Cortex |
title_sort | milnacipran remediates impulsive deficits in rats with lesions of the ventromedial prefrontal cortex |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376543/ https://www.ncbi.nlm.nih.gov/pubmed/25522418 http://dx.doi.org/10.1093/ijnp/pyu083 |
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