Transcriptional profile of brain region involved in habitual learning following methamphetamine self-administration and dopamine receptor antagonist

Methamphetamine (METH) is a powerful stimulant that has caused addiction (compulsive drug seeking and taking behavior) in millions of people world-wide. METH abuse is also associated with negative impact on the brain. One feature of addiction is uncontrollable drug seeking despite adverse consequences and becomes habitual. To mimic this in a rat model, rats with a history of METH use are given the opportunity to earn METH accompanied by aversive shocks on their feet. Rats that continue to take METH are shock-resistant (SR) and rats that reduce their METH intake are shock-sensitive (SS ).Rats that self-administered saline are controls (CT). Thereafter, rats were injected intraperitoneally with the dopamine D1 receptor antagonist, SCH23390. SCH23390 caused substantial reduction of METH taking in a dose-dependent fashion. Stopping SCH23390 administration led to re-emergence of compulsive METH taking in the shock-resistant rats.甲基苯丙胺（Methamphetamine, METH）是一种强效中枢兴奋剂，已在全球范围内导致数百万人出现成瘾行为（即强迫性觅药与用药行为）。甲基苯丙胺滥用还会对大脑造成不良影响。成瘾的核心特征之一为即便面临不良后果仍无法控制地觅药，且行为逐渐趋于习惯化。为在大鼠模型中复现该成瘾特征，研究者为具有甲基苯丙胺暴露史的大鼠提供可自行获取甲基苯丙胺的操作条件，但同时伴随足部厌恶性电击刺激。持续摄取甲基苯丙胺的大鼠表现出电击抵抗性（shock-resistant, SR），而减少甲基苯丙胺摄入的大鼠则表现出电击敏感性（shock-sensitive, SS）；经自身给药方式摄取生理盐水的大鼠作为对照组（control, CT）。随后，研究者对所有大鼠腹腔注射多巴胺D1受体拮抗剂SCH23390。SCH23390可呈剂量依赖性显著降低大鼠的甲基苯丙胺摄取量。停止SCH23390给药后，电击抵抗性大鼠的强迫性甲基苯丙胺摄取行为再次出现。