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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >The neurokinin NK2 antagonist, saredutant, ameliorates stress-induced conditions without impairing cognition.
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The neurokinin NK2 antagonist, saredutant, ameliorates stress-induced conditions without impairing cognition.

机译：神经激肽NK2拮抗剂saredutant在不损害认知的情况下改善了压力诱发的疾病。

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The current work extends our previous findings in stress-related disorders, but also addresses the impact of a neurokinin-2 (NK2) antagonist on cognition. Besides efficacy in mood disorders, an NK2 antagonist may have the potential to lack the disinhibitory components and adverse side effects associated with existing clinical treatments. Saredutant (3-30 mg/kg, per os, p.o.) was tested for anxiolytic-like potential in three mouse models: holeboard, stress-induced hyperthermia (SIH) and four-plate. In the holeboard model saredutant (30 mg/kg) showed a trend to increase head dipping without affecting general activity. In the SIH model, saredutant demonstrated a significant reduction in stress-induced temperature at 30 mg/kg, while the number of punished crossings in the four-plate was increased at all doses tested (3-30 mg/kg). While chlordiazepoxide (CDP) demonstrated anxiolytic-like effects in these models, the adverse side effects of benzodiazepines, such as sedation, disinhibition and cognitive deficits are well-documented. Saredutant produced no detrimental effect in three models of cognition: Morris Water Maze (MWM) in rats, spontaneous alternation in a Y-maze in mice and novel objection recognition in mice. In contrast, the benzodiazepine, diazepam (DZM), produced cognitive impairments. NK2 receptor antagonists like saredutant may therefore yield beneficial effects for mood disorders without the adverse effects of current treatments.
机译：当前的工作扩展了我们先前在压力相关疾病中的发现，但也解决了神经激肽2（NK2）拮抗剂对认知的影响。除了在情绪障碍中的功效外，NK2拮抗剂还可能缺乏与现有临床治疗方法相关的去抑制成分和不良副作用。在以下三种小鼠模型中测试了Saredutant（3-30 mg / kg，每个os，p.o。）的抗焦虑样电位：孔板，压力诱发的高温（SIH）和四板。在孔板模型中，烈酒（30 mg / kg）表现出增加头浸的趋势，而不影响一般活动。在SIH模型中，致敏剂显示出在30 mg / kg时应力诱导的温度显着降低，而在所有测试剂量下（3-30 mg / kg），四孔板中惩罚性杂交的数量均增加。尽管氯二氮卓（CDP）在这些模型中显示出类似抗焦虑药的作用，但苯并二氮卓类药物的不良副作用（如镇静，抑制作用和认知缺陷）已得到充分证明。 Saredutant在三种认知模型中均未产生有害影响：大鼠的莫里斯水迷宫（MWM），小鼠的Y迷宫中的自发交替以及小鼠的新型异物识别。相反，苯二氮卓，地西epa（DZM）会产生认知障碍。 NK2受体拮抗剂，如香辣味剂，可能因此对情绪障碍产生有益的作用，而没有当前疗法的不利影响。

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