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注意缺陷多动障碍大鼠模型中哌甲酯和蔗糖颗粒自我给药的品系差异

Strain differences in self-administration of methylphenidate and sucrose pellets in a rat model of attention-deficit hyperactivity disorder.

作者信息

Marusich Julie A, McCuddy William Travis, Beckmann Joshua S, Gipson Cassandra D, Bardo Michael T

机构信息

Center for Drug Abuse Research Translation, University of Kentucky, Kentucky, USA.

出版信息

Behav Pharmacol. 2011 Dec;22(8):794-804. doi: 10.1097/FBP.0b013e32834d623e.

Abstract

Despite its abuse potential, methylphenidate (MPH) is widely prescribed for treatment of attention-deficit hyperactivity disorder (ADHD). The purpose of the present study was to examine MPH self-administration in a rat model of ADHD. Experiment 1 examined the acquisition of MPH self-administration and assessed the MPH dose-effect curve in spontaneously hypertensive rats (SHR), an inbred rat model of ADHD, Wistar Kyotos (WKY), the progenitor strain for SHR, and Sprague-Dawley (SD), an outbred control strain. Experiment 2 replicated Experiment 1, but replaced MPH infusions with sucrose pellets. Initial acquisition of MPH self-administration was greater in SHR and SD than WKY. However, with extended training using an incrementing fixed ratio schedule SHR and WKY did not differ in responding for MPH using the training dose (0.3 mg/kg/infusion) or other unit doses, except that SHR showed greater responding than WKY at 0.1 mg/kg/infusion. SHR also showed greater acquisition and maintenance of sucrose-reinforced responding compared with both WKY and SD. Greater initial acquisition of MPH self-administration in SHR than WKY may not be due to a strain-specific difference in sensitivity to the reinforcing effect of MPH.

摘要

尽管哌甲酯(MPH)具有滥用可能性,但它仍被广泛用于治疗注意力缺陷多动障碍(ADHD)。本研究的目的是在ADHD大鼠模型中检测MPH的自我给药情况。实验1检测了MPH自我给药的习得过程,并评估了自发性高血压大鼠(SHR,一种ADHD近交系大鼠模型)、SHR的祖系Wistar Kyoto大鼠(WKY)以及远交对照品系Sprague-Dawley大鼠(SD)的MPH剂量效应曲线。实验2重复了实验1,但用蔗糖颗粒替代了MPH输注。SHR和SD对MPH自我给药的初始习得比WKY更强。然而,在使用递增固定比率程序进行延长训练后,SHR和WKY在使用训练剂量(0.3mg/kg/输注)或其他单位剂量时对MPH的反应没有差异,只是SHR在0.1mg/kg/输注时的反应比WKY更强。与WKY和SD相比,SHR在蔗糖强化反应的习得和维持方面也表现得更强。SHR对MPH自我给药的初始习得比WKY更强,这可能并非由于对MPH强化作用的敏感性存在品系特异性差异。

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