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注意缺陷多动障碍动物模型(自发性高血压大鼠)中的哌甲酯自我给药及条件性位置偏爱

Methylphenidate self-administration and conditioned place preference in an animal model of attention-deficit hyperactivity disorder: the spontaneously hypertensive rat.

作者信息

dela Peńa Ike C, Ahn Hyung Seok, Choi Ji Young, Shin Chan Young, Ryu Jong Hoon, Cheong Jae Hoon

机构信息

Uimyung Research Institute for Neuroscience, Sahmyook University, Nowon-gu, Seoul, Korea.

出版信息

Behav Pharmacol. 2011 Feb;22(1):31-9. doi: 10.1097/FBP.0b013e328342503a.

Abstract

The abuse potential of methylphenidate, the most commonly used drug for attention-deficit hyperactivity disorder (ADHD), has been shown in many studies. However, it is not yet known whether methylphenidate has reinforcing or rewarding effects in any animal model of ADHD. In this study, we investigated whether methylphenidate facilitates self-administration and induces conditioned place preference in the spontaneously hypertensive rat (SHR), the most validated animal model of ADHD. We also explored whether the behavioral responses of SHR differ from those of Wistar rats, the strain representing the 'normal' heterogeneous population. ADHD is highly prevalent among adolescents, such that behavioral assays should be conducted in adolescent SHR. In line with this, we carried out conditioned place preference tests in adolescent SHR and Wistar rats and observed strain and age-related differences in behavioral responses to the motivational effects of methylphenidate. Self-administration tests confirmed the reinforcing effect of methylphenidate in SHR, and showed that, in FR2 and FR3 schedules, SHR responded more to methylphenidate infusions than the Wistar rats. In conditioned place preference tests, both strains responded similarly to the rewarding effects of methylphenidate. However, it was found that adolescence also alters the euphorigenic effects of methylphenidate, most especially in SHR. The implications of these findings are discussed.

摘要

哌甲酯是治疗注意力缺陷多动障碍(ADHD)最常用的药物,许多研究已证实其具有滥用可能性。然而,在任何ADHD动物模型中,哌甲酯是否具有强化或奖赏作用尚不清楚。在本研究中,我们调查了哌甲酯是否能促进自发高血压大鼠(SHR,一种最有效的ADHD动物模型)的自我给药并诱导其条件性位置偏爱。我们还探究了SHR的行为反应是否与代表“正常”异质群体的Wistar大鼠不同。ADHD在青少年中非常普遍,因此行为分析应在青春期SHR中进行。与此一致,我们在青春期SHR和Wistar大鼠中进行了条件性位置偏爱测试,并观察到对哌甲酯动机效应的行为反应存在品系和年龄相关差异。自我给药测试证实了哌甲酯对SHR的强化作用,并表明在FR2和FR3给药方案中,SHR对哌甲酯输注的反应比Wistar大鼠更强烈。在条件性位置偏爱测试中,两个品系对哌甲酯奖赏效应的反应相似。然而,研究发现青春期也会改变哌甲酯的致欣快作用,在SHR中尤为明显。本文讨论了这些发现的意义。

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