The Second Affiliated Hospital, Xinxiang Medical University, Jianshe Road #388, Muye District, Xinxiang City, Henan Province, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, 27th Taiping Road, Beijing, 100850, China.
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, 27th Taiping Road, Beijing, 100850, China.
Eur J Pharmacol. 2019 Dec 15;865:172671. doi: 10.1016/j.ejphar.2019.172671. Epub 2019 Sep 19.
Methamphetamine (METH) addiction has been widely spread and caused severe problems both in society and public health in recent years, but there is a shortage of medication available. The naltrexone (NTX) as a non-selective opioid receptor antagonist has been widely applied to treat alcohol addiction and the relapse to opioid addiction after detoxification. In the present study, we investigated the potent pharmacotherapeutic effect of NTX in attenuating relapse to drug-seeking behavior in the METH self-administration and conditioned place preference (CPP) in rats. The results showed that acute intragastrical administration of NTX (40 mg/kg) significantly reduced cue-induced drug-seeking behavior after extinction training. The similar inhibition effect was observed in the CPP model, that the intragastrical administration of NTX (30 mg/kg) significantly disrupted the reactivation induced by intraperitoneal injection of METH (0.5 mg/kg) after the extinction training process. However, respective intragastrical administration of NTX (20 or 40 mg/kg) failed to alter the dose-response curve of METH under fixed ratio 2 program and intraperitoneal injection of METH (1.0 mg/kg)-induced reinstatement in rats self-administration. Overall, our findings suggest that NTX has the pharmacotherapeutic potential in reducing the relapse of METH addiction, which deserves further investigation as a promising medication for the treatment of METH addiction.
近年来，冰毒（METH）成瘾在社会和公共卫生方面广泛传播，造成了严重的问题，但可供使用的药物却很短缺。纳曲酮（NTX）作为一种非选择性阿片受体拮抗剂，已广泛应用于治疗酒精成瘾和脱毒后对阿片类药物的复吸。在本研究中，我们研究了 NTX 在减轻 METH 自身给药和条件性位置偏爱（CPP）大鼠觅药行为复吸中的有效药物治疗作用。结果表明，急性灌胃给予 NTX（40mg/kg）可显著减少消退训练后线索诱导的觅药行为。在 CPP 模型中也观察到类似的抑制作用，即灌胃给予 NTX（30mg/kg）可显著破坏消退训练过程后 METH（0.5mg/kg，腹腔注射）诱导的再激活。然而，分别灌胃给予 NTX（20 或 40mg/kg）未能改变固定比率 2 程序下 METH 的剂量-反应曲线，也未能改变 METH（1.0mg/kg，腹腔注射）诱导的大鼠自身给药复吸。总的来说，我们的研究结果表明，NTX 具有减少 METH 成瘾复吸的药物治疗潜力，值得进一步研究，作为治疗 METH 成瘾的一种有前途的药物。
