Voigt Robin M, Herrold Amy A, Napier T Celeste
Rush University Medical Center, 1735 W. Harrison St., Chicago, IL 60612, USA.
Behav Neurosci. 2011 Apr;125(2):261-7. doi: 10.1037/a0022893.
The powerful, long-lasting association between the rewarding effects of a drug and contextual cues associated with drug administration can be studied using conditioned place preference (CPP). The GABA(B) receptor agonist baclofen facilitates the extinction of morphine-induced CPP in mice. The current study extended this work by determining if baclofen could enhance the extinction of methamphetamine (Meth) CPP. CPP was established using a six-day conditioning protocol wherein Meth-pairings were alternated with saline-pairings. Rats were subsequently administered baclofen (2 mg/kg i.p. or vehicle) immediately after each daily forced extinction session, which consisted of a saline injection immediately prior to being placed into the previously Meth- or saline-paired chamber. One extinction training cycle, consisted of six once-daily forced extinction sessions, mimicking the alternating procedure established during conditioning, followed by a test for preference (Ext test). CPP persisted for at least four extinction cycles in vehicle-treated rats. In contrast, CPP was inhibited following a single extinction training cycle. These data indicate that Meth-induced CPP was resistant to extinction, but extinction training was rendered effective when the training was combined with baclofen. These findings converge with the prior demonstration of baclofen facilitating the extinction of morphine-induced CPP indicating that GABA(B) receptor actions are independent of the primary (unconditioned) stimulus (i.e., the opiate or the stimulant) and likely reflect mechanisms engaged by extinction learning processes per se. Thus, baclofen administered in conjunction with extinction training may be of value for addiction therapy regardless of the class of drug being abused.
药物的奖赏效应与给药相关的情境线索之间强大而持久的关联可以通过条件性位置偏爱（CPP）来研究。GABA(B)受体激动剂巴氯芬可促进小鼠吗啡诱导的CPP的消退。本研究通过确定巴氯芬是否能增强甲基苯丙胺（冰毒）CPP的消退来扩展这项工作。使用为期六天的条件化方案建立CPP，其中甲基苯丙胺配对与生理盐水配对交替进行。随后，在每天的强制消退训练后立即给大鼠腹腔注射巴氯芬（2mg/kg）或赋形剂，强制消退训练包括在放入先前与甲基苯丙胺或生理盐水配对的实验箱之前立即注射生理盐水。一个消退训练周期包括六个每天一次的强制消退训练，模仿条件化过程中建立的交替程序，然后进行偏爱测试（消退测试）。在接受赋形剂治疗的大鼠中，CPP持续至少四个消退周期。相比之下，单次消退训练周期后CPP受到抑制。这些数据表明，甲基苯丙胺诱导的CPP对消退有抗性，但当训练与巴氯芬联合使用时，消退训练变得有效。这些发现与之前关于巴氯芬促进吗啡诱导的CPP消退的证明一致，表明GABA(B)受体的作用独立于主要（非条件）刺激（即阿片类药物或兴奋剂），可能反映了消退学习过程本身所涉及的机制。因此，无论滥用的药物类别如何，与消退训练联合使用的巴氯芬可能对成瘾治疗有价值。
