Preclinical Pharmacology Section, NIH/NIDA Intramural Research Program, 251 Bayview Boulevard, Suite 200, Baltimore, MD 21224, USA.
Exp Clin Psychopharmacol. 2011 Feb;19(1):1-10. doi: 10.1037/a0022432.
The effectiveness of methadone as a treatment for opioid abuse and nicotine preparations as treatments for tobacco smoking has led to an interest in developing a similar strategy for treating psychostimulant abuse. The current study investigated the effects of three such potential therapies on intravenous methamphetamine self-administration (1 - 30 μg/kg/injection) in rhesus monkeys. When given as a presession intramuscular injection, a high dose of methamphetamine (1.0 mg/kg) decreased intravenous methamphetamine self-administration but did not affect responding for a food reinforcer during the same sessions. However, the dose of intramuscular methamphetamine required to reduce intravenous methamphetamine self-administration exceeded the cumulative amount taken during a typical self-administration session, and pretreatment with a low dose of methamphetamine (0.3 mg/kg) actually increased self-administration in some monkeys at the lower self-administration dose. Like pretreatment with methamphetamine, pretreatment with bupropion (3.2 mg/kg) decreased methamphetamine self-administration but did not affect responding for food. Pretreatment with methylphenidate (0.56 mg/kg) did not significantly alter methamphetamine self-administration. These results suggest that some agonist-like agents can decrease methamphetamine self-administration. Although the most robust effects occurred with a high dose of methamphetamine, safety and abuse liability considerations suggest that bupropion should also be considered for further evaluation as a methamphetamine addiction treatment.
美沙酮作为治疗阿片类药物滥用和尼古丁制剂作为治疗吸烟的方法的有效性，促使人们产生了开发类似策略来治疗精神兴奋剂滥用的兴趣。本研究调查了三种潜在疗法对恒河猴静脉内甲基苯丙胺自我给药（1-30μg/kg/注射）的影响。当作为课前肌内注射给予时，高剂量的甲基苯丙胺（1.0mg/kg）降低了静脉内甲基苯丙胺自我给药，但在相同的疗程中不影响食物强化物的反应。然而，降低静脉内甲基苯丙胺自我给药所需的肌内甲基苯丙胺剂量超过了典型自我给药疗程中摄入的累积量，并且低剂量的甲基苯丙胺（0.3mg/kg）预处理实际上在一些猴子中增加了较低自我给药剂量下的自我给药。与甲基苯丙胺预处理一样，安非他酮（3.2mg/kg）预处理降低了甲基苯丙胺的自我给药，但不影响食物的反应。哌甲酯（0.56mg/kg）预处理对甲基苯丙胺的自我给药没有显著影响。这些结果表明，一些类似激动剂的药物可以降低甲基苯丙胺的自我给药。尽管最显著的效果发生在高剂量的甲基苯丙胺，但安全性和滥用倾向考虑表明，安非他酮也应被考虑进一步评估作为甲基苯丙胺成瘾的治疗方法。
