Mirtazapine alters cue-associated methamphetamine seeking in rats.
Mirtazapine alters cue-associated methamphetamine seeking in rats.
复制标题
Mirtazapine改变了在大鼠中寻求与提示相关的甲基苯丙胺。
DOI：
10.1016/j.biopsych.2010.09.032
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发表时间：
2011-02-01
影响因子：
10.6
通讯作者：
Napier, T. Celeste
中科院分区：
文献类型：
--
作者：
Graves, Steven M.;Napier, T. Celeste
甲基苯丙胺（METH）是一种强效精神兴奋剂，重复使用可导致药物滥用障碍。退缩的人很容易复发，这可能是驱动的，至少部分是由一个高反应的METH相关的线索，可以促使METH寻求。目前迫切需要确定临床有效的药物治疗甲基苯丙胺滥用。米氮平（Remeron®）是一种非典型抗抑郁药，可拮抗活化的去甲肾上腺素α2、组胺1-羟色胺（5-HT）2A/C和5-HT 3受体。这种药理学特征促使我们对其预防复发的潜力感兴趣。目前的研究测试了假设，米氮平会减弱训练自我管理的大鼠的甲基苯丙胺寻求。大鼠接受训练，以在压迫性操作任务中自我施用METH。米氮平对寻求甲基的影响是通过评估杠杆压在存在的线索，以前与甲基有关，但在没有甲基强化。使用了两种范例：提示反应性，其中大鼠不经历灭绝训练，以及灭绝后提示诱导的恢复范例。米氮平（5.0mg/kg）预处理在线索反应性和线索诱导的恢复测试的前15分钟内减少了约50%的METH寻求。该米氮平剂量对运动表现无显著影响。这项研究揭示了线索反应性和线索诱导的恢复程序的重叠性质，并提供了临床前证据表明，米氮平可以减弱寻求甲基苯丙胺的行为。
Methamphetamine (METH) is a potent psychostimulant, repeated use of which can result in a substance abuse disorder. Withdrawn individuals are highly prone to relapse which may be driven, at least in part, by a hyper-responsivity to METH-associated cues that can prompt METH-seeking. There is a critical need to identify clinically efficacious pharmacotherapies for METH abuse. Mirtazapine (Remeron®) is an atypical antidepressant, that antagonizes activated norepinephrineα2, histamine1 serotonin (5-HT)2A/C, and 5-HT3 receptors. This pharmacological profile prompted our interest in its potential for preventing relapse to METH-taking. The current study tested the hypothesis that mirtazapine would attenuate METH-seeking in rats trained to self-administer METH. Rats were trained to self-administer METH in a lever-pressing operant task. The effect of mirtazapine on METH-seeking was determined by evaluating lever pressing in the presence of cues previously associated with METH, but in the absence of METH reinforcement. Two paradigms were utilized: cue reactivity, wherein rats do not undergo extinction training, and a cue-induced reinstatement paradigm after extinction. Mirtazapine (5.0mg/kg) pretreatment reduced METH-seeking by ~50% in the first 15min of cue reactivity and cue-induced reinstatement testing. This mirtazapine dose did not significantly impact motor performance. This study revealed the overlapping nature of cue reactivity and cue-induced reinstatement procedures and provided preclinical evidence that mirtazapine can attenuate METH-seeking behavior.
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影响因子：
3.4
作者：
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通讯作者：
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