Shelton Keith L, Beardsley Patrick M
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond VA 23298-0613, United States.
Pharmacol Biochem Behav. 2008 Sep;90(3):434-40. doi: 10.1016/j.pbb.2008.03.028. Epub 2008 Apr 4.
The purpose of the present study was to examine the impact of drug-paired cues on methamphetamine reinstatement. Three groups of rats were trained to self-administer 0.1 mg/kg/infusion methamphetamine. Each methamphetamine infusion was accompanied by a 6 s flashing light+tone stimulus (cues). After training, the groups were then given 12, daily extinction sessions either with or without response-contingent drug-paired cues and then tested for 1 mg/kg i.p. methamphetamine priming-induced reinstatement either with or without cues. Methamphetamine priming significantly reinstated drug-appropriate responding regardless of whether response-contingent cues were omitted during both extinction and testing, presented during both extinction and testing, or omitted during extinction but presented during reinstatement testing. The group in which cues were omitted during extinction and presented during reinstatement exhibited significantly greater reinstatement than did the other two groups. A separate group of rats was also tested demonstrating that response-contingent presentation of previously methamphetamine-paired cues alone, without methamphetamine priming, significantly reinstated drug-appropriate responding. These data show that methamphetamine priming produces a robust reinstatement effect which can be influenced by drug-paired cues.
本研究的目的是检验药物配对线索对甲基苯丙胺复吸的影响。三组大鼠被训练自行注射0.1毫克/千克/次的甲基苯丙胺。每次注射甲基苯丙胺时伴有6秒的闪光+音调刺激(线索)。训练后,这些组随后每天进行12次消退训练,训练过程中有的组有与反应相关的药物配对线索,有的组没有,然后分别在有或没有线索的情况下,对腹腔注射1毫克/千克甲基苯丙胺引发的复吸进行测试。无论在消退训练和测试期间是否省略与反应相关的线索,还是在消退训练和测试期间都呈现线索,又或是在消退训练期间省略但在复吸测试期间呈现线索,甲基苯丙胺引发均显著恢复了与药物相关的反应。在消退训练期间省略线索而在复吸测试期间呈现线索的组,其复吸程度显著高于其他两组。另外一组大鼠也进行了测试,结果表明,仅呈现先前与甲基苯丙胺配对的线索(无甲基苯丙胺引发),且该线索与反应相关时,也能显著恢复与药物相关的反应。这些数据表明,甲基苯丙胺引发会产生强大的复吸效应,且该效应会受到药物配对线索的影响。