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[作为注意缺陷多动障碍动物模型的幼年易卒中型自发性高血压大鼠的行为学和药理学研究]

[Behavioral and pharmacological studies of juvenile stroke-prone spontaneously hypertensive rats as an animal model of attention-deficit/hyperactivity disorder].

作者信息

Ueno Ken-ichi, Togashi Hiroko, Yoshioka Mitsuhiro

机构信息

Department of Pharmacology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-8638 Japan.

出版信息

Nihon Shinkei Seishin Yakurigaku Zasshi. 2003 Feb;23(1):47-55.

Abstract

The present study was undertaken to evaluate juvenile stroke-prone spontaneously hypertensive rats (SHRSP) as an animal model of attention-deficit/hyperactivity disorder (AD/HD). Juvenile SHRSP showed significant increases in horizontal ambulatory activity and vertical rearing activity in the open field as compared with genetic control Wistar-Kyoto rats (WKY). Anxiety-related behavior assessed by elevated plus-maze as an index of impulsivity, the entries into open arms and the spent time in the open arms of SHRSP were significantly higher than those of WKY. Spontaneous alternation behavior requiring attention and working memory in the Y-maze was significantly impaired in male, but not female, SHRSP when compared with sex-matched WKY. Hippocampal long-term potentiation formation, a cellular model of learning and memory, was not impaired in SHRSP. Methylphenidate, a first choice psychostimulant for AD/HD, significantly alleviated the hyperactivity in SHRSP. However, intense impulsivity of SHRSP was not improved by methylphenidate. Methylphenidate dose-dependently and significantly ameliorated the impaired spontaneous alteration behavior in male SHRSP. These results suggest that juvenile male SHRSP manifest problematic behavior resembling ADHD, namely inattention, hyperactivity and impulsivity. Methylphenidate alleviates the behavioral symptoms of hyperactivity and inattention. Thus, juvenile male SHRSP might be a useful behavioral animal model of AD/HD, from behavioral and pharmacological perspectives.

摘要

本研究旨在评估易患中风的幼年自发性高血压大鼠(SHRSP)作为注意力缺陷多动障碍(AD/HD)的动物模型。与基因对照的Wistar-Kyoto大鼠(WKY)相比,幼年SHRSP在旷场实验中的水平移动活动和垂直站立活动显著增加。以高架十字迷宫评估的与焦虑相关的行为作为冲动性指标,SHRSP进入开放臂的次数和在开放臂中花费的时间显著高于WKY。与性别匹配的WKY相比,雄性而非雌性SHRSP在Y迷宫中需要注意力和工作记忆的自发交替行为显著受损。学习和记忆的细胞模型——海马体长期增强形成在SHRSP中未受损。哌甲酯是治疗AD/HD的首选精神兴奋剂,它显著减轻了SHRSP的多动症状。然而,哌甲酯并未改善SHRSP强烈的冲动性。哌甲酯剂量依赖性地显著改善了雄性SHRSP受损的自发交替行为。这些结果表明,幼年雄性SHRSP表现出类似于ADHD的问题行为,即注意力不集中、多动和冲动。哌甲酯减轻了多动和注意力不集中的行为症状。因此,从行为和药理学角度来看,幼年雄性SHRSP可能是一种有用的AD/HD行为动物模型。

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