Sasamori Hitomi, Ohmura Yu, Kubo Takuya, Yoshida Takayuki, Yoshioka Mitsuhiro
Hokkaido University School of Medicine, N15 W7 Kita-ku, Sapporo 060-8638, Japan.
Department of Neuropharmacology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15 W7 Kita-ku, Sapporo 060-8638, Japan.
Behav Brain Res. 2018 May 2;343:61-70. doi: 10.1016/j.bbr.2018.01.014. Epub 2018 Jan 31.
Immaturity in impulse control among adolescents could result in substance abuse, criminal involvement, and suicide. The brains of adolescents and adults are anatomically, neurophysiologically, and pharmacologically different. Therefore, preclinical models of adolescent impulsivity are required to screen drugs for adolescents and elucidate the neural mechanisms underlying age-related differences in impulsivity. The conventional 3- or 5-choice serial reaction time task, which is a widely used task to assess impulsivity in adult rodents, cannot be used for young mice because of two technical problems: impaired growth caused by food restriction and the very long training duration. To overcome these problems, we altered the conventional training process, optimizing the degree of food restriction for young animals and shortening the training duration. We found that almost all basal performance levels were similar between the novel and conventional procedures. We also confirmed the pharmacological validity of our results: the 5-hydroxytryptamine 2C (5-HT) receptor agonist Ro60-0175 (0.6 mg/kg, subcutaneous) reduced the occurrence of premature responses, whereas the 5-HT receptor antagonist SB242084 (0.5 mg/kg intraperitoneal) increased their occurrence, consistent with results of previous studies using conventional procedures. Furthermore, we detected age-related differences in impulsivity using the novel procedure: adolescent mice were found to be more impulsive than adult mice, congruent with the results of human studies. Thus, the new procedure enables the assessment of impulsivity in adolescent mice and facilitates a better understanding of the neurophysiological/pharmacological properties of adolescents.
青少年冲动控制方面的不成熟可能导致药物滥用、犯罪行为和自杀。青少年和成年人的大脑在解剖学、神经生理学和药理学上存在差异。因此，需要青少年冲动性的临床前模型来筛选适合青少年的药物，并阐明冲动性方面与年龄相关差异的神经机制。传统的3选或5选连续反应时任务是评估成年啮齿动物冲动性的常用任务，但由于两个技术问题不能用于幼鼠：食物限制导致生长受损以及训练持续时间过长。为克服这些问题，我们改变了传统的训练过程，优化了幼龄动物的食物限制程度并缩短了训练持续时间。我们发现新方法和传统方法之间几乎所有的基础表现水平都相似。我们还证实了结果的药理学有效性：5-羟色胺2C（5-HT）受体激动剂Ro60-0175（0.6mg/kg，皮下注射）减少了过早反应的发生，而5-HT受体拮抗剂SB242084（0.5mg/kg腹腔注射）增加了过早反应的发生，这与之前使用传统方法的研究结果一致。此外，我们使用新方法检测到了冲动性方面与年龄相关的差异：发现青春期小鼠比成年小鼠更冲动，这与人类研究结果一致。因此，新方法能够评估青春期小鼠的冲动性，并有助于更好地理解青少年的神经生理学/药理学特性。
