Kelamangalath Lakshmi, Swant Jarod, Stramiello Michael, Wagner John J
Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602-7389, USA.
Behav Brain Res. 2007 Dec 28;185(2):119-28. doi: 10.1016/j.bbr.2007.08.001. Epub 2007 Aug 6.
Although the process of extinction has been well documented for various forms of behavioral responses, the effects of extinction on the reinstatement of drug-seeking behavior are relatively understudied. In this report, the effectiveness of an extinction training protocol to reduce primed reinstatement responses was compared with the effectiveness of an equivalent period of enforced abstinence. We found that extinction training performed in the drug taking environment significantly reduced reinstatement behavior subsequently primed by either contextual cues, conditioned cues, or cocaine infusion. The ability of extinction to reduce cocaine primed reinstatement was blocked by the systemic administration of the competitive NMDAR antagonist ((+/-)CPP, 5mg/kg i.p.) administered prior to each extinction training session. Interestingly, this pharmacological intervention had no impact on the effectiveness of extinction to reduce drug-seeking behavior primed by either contextual cues or conditioned cues. These results suggest that an extinction training experience involves multiple mechanisms that can be dissociated into nonNMDAR and NMDAR dependent components with respect to the type of reinstatement (i.e. context-, conditioned stimuli (CS)-, or drug-induced) being assessed.
尽管消退过程在各种行为反应形式中已有充分记录，但消退对药物寻求行为恢复的影响相对研究较少。在本报告中，将一种消退训练方案减少引发的恢复反应的效果与同等时长的强制戒断效果进行了比较。我们发现，在药物服用环境中进行的消退训练显著降低了随后由情境线索、条件线索或可卡因注射引发的恢复行为。在每次消退训练前全身给予竞争性NMDAR拮抗剂（（±）CPP，5mg/kg腹腔注射），可阻断消退降低可卡因引发的恢复行为的能力。有趣的是，这种药理学干预对消退减少由情境线索或条件线索引发的药物寻求行为的效果没有影响。这些结果表明，消退训练经历涉及多种机制，就所评估的恢复类型（即情境、条件刺激（CS）或药物诱导）而言，这些机制可分为非NMDAR和NMDAR依赖成分。
