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Title
  • en Milnacipran Remediates Impulsive Deficits in Rats with Lesions of the Ventromedial Prefrontal Cortex
Creator
Accessrights open access
Rights
Subject
  • Other en inhibitory control
  • Other en infralimbic cortex
  • Other en spinogenesis
  • Other en impulsive behavior
  • Other en BDNF
  • NDC 490
Description
  • Abstract en 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 10 mg/kg/d x 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.
Publisher en Oxford University Press
Date
    Issued2015-03
Language
  • eng
Resource Type journal article
Version Type VoR
Identifier HDL http://hdl.handle.net/2115/59283
Relation
  • isIdenticalTo DOI https://doi.org/10.1093/ijnp/pyu083
Journal
    • PISSN 1461-1457
      • en International journal of neuropsychopharmacology
      • Volume Number18 Issue Number5 Page Startpyu083
File
Oaidate 2023-07-26