Milnacipran remediates impulsive deficits in rats with lesions of the ventromedial prefrontal cortex
Milnacipran remediates impulsive deficits in rats with lesions of the ventromedial prefrontal cortex
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米那普仑可修复腹内侧前额叶皮层损伤大鼠的冲动缺陷
DOI：
10.1093/ijnp/pyu083
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Yoshioka M
中科院分区：
文献类型：
--
作者：
Tsutsui-Kimura I;Yoshida T;Ohmura Y;Izumi T;Yoshioka M
背景在精神疾病中经常观察到冲动控制缺陷，其中观察到前额皮质异常，包括注意力缺陷/多动障碍和双相情感障碍。我们最近发现米那普仑（一种血清素/去甲肾上腺素再摄取抑制剂）可以抑制正常大鼠的冲动行为。然而，米那普仑是否能够抑制腹内侧前额叶皮质损伤大鼠的冲动行为（其功能与人类前额叶皮质相当）仍不清楚。 方法使用喹啉酸对先前接受过三项选择系列反应时间任务训练的大鼠进行腹内侧前额叶皮质选择性损伤。假手术大鼠接受磷酸盐缓冲盐水。经过一段时间的恢复后，在进行三项选择任务测试前 60 分钟口服米那普仑（0 或 10mg/kg/d × 14 天）。停药7天后进行Western blotting、免疫组化、电生理分析和形态学分析。结果腹内侧前额叶皮层损伤诱发冲动缺陷，重复米那普仑在给药期间和停药后均可改善冲动缺陷。重复米那普仑可修复腹内侧前额叶皮层损伤大鼠腹内侧前额叶皮层中少数幸存神经元的成熟脑源性神经营养因子和突触后密度 95、树突棘密度和兴奋性电流的蛋白质水平。结论本研究的结果表明，米那普仑治疗可能是治疗与缺乏冲动控制相关的精神疾病的新策略。
BackgroundDeficits 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.MethodsSelective 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.ResultsLesions 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.ConclusionsThe 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.