Chronic modafinil effects on drug-seeking following methamphetamine self-administration in rats.
Chronic modafinil effects on drug-seeking following methamphetamine self-administration in rats.
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DOI：
10.1017/s1461145711000988
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发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
See RE
中科院分区：
文献类型：
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作者：
Reichel CM;See RE
认知增强药物莫达非尼（Provigil®）的急性给药减少了从每日自我给药中戒断后的甲基苯丙胺（甲基）寻求。然而，莫达非尼对长期治疗后寻求冰毒的临床相关影响尚未探讨。在这里，我们确定了莫达非尼的影响，寻求长期的日常治疗后，在灭绝或禁欲后，甲基自我管理。大鼠在每天2小时的会议期间自行静脉注射冰毒，持续14天，然后进行消退会议或禁欲。在此期间，大鼠每天接受媒介物、30或100 mg/kg莫达非尼注射，然后在早期和晚期戒断时间点通过线索、甲基引发和上下文诱导的恢复测试甲基寻求。我们发现，慢性莫达非尼衰减复发的甲基配对的情况下，减少条件线索诱导和甲基引发的恢复，并导致持久减少甲基寻求即使在停止治疗后。此外，我们确定在维持自我给药期间，只有非常高剂量的莫达非尼（300 mg/kg）对甲基摄入量有影响。这些结果验证并扩展了临床和临床前发现，莫达非尼可能是一种可行的治疗选择。
Acute administration of the cognitive enhancing drug, modafinil (Provigil®), reduces methamphetamine (meth) seeking following withdrawal from daily self-administration. However, the more clinically relevant effects of modafinil on meth-seeking after chronic treatment have not been explored. Here, we determined the impact of modafinil on meth-seeking after chronic daily treatment during extinction or abstinence following meth self-administration. Rats self-administered intravenous meth during daily 2-h sessions for 14 days, followed by extinction sessions or abstinence. During this period, rats received daily injections of vehicle, 30, or 100 mg/kg modafinil and were then tested for meth-seeking via cue, meth-primed, and context-induced reinstatement at early and late withdrawal time points. We found that chronic modafinil attenuated relapse to a meth-paired context, decreased conditioned cue-induced and meth-primed reinstatement, and resulted in enduring reductions in meth-seeking even after discontinuation of treatment. Additionally, we determined that only a very high dose of modafinil (300 mg/kg) during maintenance of self-administration had an impact on meth intake. These results validate and extend clinical and preclinical findings that modafinil may be a viable treatment option for meth addiction.