下边缘皮质PKMζ在直接消退训练和唤起-消退训练两种模式中的作用  

INVOVLEMENT OF INFRALIMBIC PKMζ IN THE PROCEDURES OF EXTINCTION AND RETRIEVAL-EXTINCTION

作　　者：薛丽芬[1] 薛言学[2] 罗宜孝[2] 陆林[2] 

机构地区：[1]重庆医科大学附属第一医院,重庆400016 [2]北京大学中国药物依赖性研究所,北京100191

出　　处：《中国药物依赖性杂志》2013年第4期248-254,共7页Chinese Journal of Drug Dependence

基　　金：国家自然科学基金(91132716)

摘　　要：目的獉獉:唤起之后在再巩固的时间窗内进行消退训练能够降低可卡因引起的觅药行为的复燃,利用蛋白激酶Mζ(PKMζ)的抑制剂ZIP探讨其相关的分子机制。方法獉獉:采用大鼠自身给药(SA)模型,用核团微注射方法。结果獉獉:大鼠获得了稳定的可卡因自身给药行为后进行12 d的消退训练,达到消退标准之后24 h给予核团微注射干预。干预48 h之后腹腔注射可卡因。与直接消退训练组相比,再巩固时间窗内消退训练(唤起-消退)组能够明显降低可卡因诱导的觅药行为的复燃;下边缘皮质微注射PKMζ抑制剂ZIP可以增强直接消退训练组以及唤起-消退训练组可卡因诱导的复燃行为。结论獉獉:唤起之后在再巩固的时间窗内进行消退训练能够有效降低药物渴求行为,而下边缘皮质PKMζ同时参与了唤起-消退训练模式和直接消退训练模式,表明唤起-消退训练和直接消退训练可能存在部分相同的神经基础。Objective： Retrieval- extinction procedure could attenuate cocaine- priming- induced reinstatement of drug seeking. In the present study ,we used ZIP to investigate the role of protein kinase M ~ （PKM~） in infralimbic cortex subregion of medial prefrontal cortex （ IL - mPFC ） in this memory process. Met.h？.ds..： An intravenous cocaine self - administration （ SA ） procedure in rats and intracranial injections were used in this study. Resu/ts： After acquisition of stable cocaine self - administration, the rats were exposed to extinction training until they reach the criterion. Twenty - four hours later, the rats were injected with PKM~ inhibiter ZIP or scrambled - ZIP into the infralimbic cortex. Two day later, the rats were given a non -contingent priming injections of cocaine and priming test. Compared with 195 -min extinction training groups, retrieval -extinction training group showed attenuated cocaine - induced reinstatement of SA behavior. However, injection of ZIP other than sZIP into IL could enhance the priming - induced drug - seeking behavior in both extinction and retrieval - extinction groups. Conclusion.：Extinction within reconsolidation time window prevent relapse to drug - seeking behavior, and PKM activity in the infralimbic cortex may be involved in both extinction and retrieval - extinction procedures, which indicates that extinction within specific time window after retrieval may prevent relapse to drug- seeking behavior via enhancing extinction.

关 键 词：下边缘皮质 PKMζ 唤起-消退 奖赏记忆 可卡因 

分 类 号：R322.81[医药卫生—人体解剖和组织胚胎学]