Basolateral amygdala involvement in memory reconsolidation processes that facilitate drug context-induced cocaine seeking.
Basolateral amygdala involvement in memory reconsolidation processes that facilitate drug context-induced cocaine seeking.
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DOI：
10.1111/j.1460-9568.2009.06888.x
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发表时间：
2009-09
期刊：
影响因子：
--
通讯作者：
Su ZI
中科院分区：
文献类型：
--
作者：
Fuchs RA;Bell GH;Ramirez DR;Eaddy JL;Su ZI
从成瘾治疗的角度来看，了解假定的记忆稳定过程的神经生物学基础是非常有趣的，这些记忆稳定过程在长期记忆中保持了上下文-反应-可卡因的关联，并且是成瘾行为的上下文控制的基础。使用一个工具性的动物模型的上下文药物复发，我们表明，蛋白质合成抑制剂，茴香霉素，管理到基底外侧杏仁核（BLA）后立即有限（15或60分钟）重新暴露于先前可卡因配对的上下文，随后破坏的能力，先前可卡因配对的上下文恢复熄灭可卡因寻求行为相对于车辆。与BLA介导的记忆再巩固缺陷一致，在“无再激活”对照组中未观察到可卡因寻求行为的类似损害，所述对照组在（重新）暴露于新的未配对或抑制配对背景后将茴香霉素接受到BLA中，也未在神经解剖学对照组中观察到可卡因寻求行为的类似损害，所述对照组在重新暴露于可卡因配对背景后将茴香霉素接受到后尾壳核-壳核，背侧邻近BLA。此外，在短暂（5分钟）或广泛（120分钟）重新暴露于可卡因配对环境（足以消除溶剂对照组中的可卡因寻求行为）后，将茴香霉素施用于BLA也未能改变反应。总之，这些发现表明，在没有可卡因强化的情况下重新暴露于可卡因配对的环境足以触发支持未来药物寻求行为的记忆重新巩固过程。药物相关记忆再激活的存在和持续时间严重影响BLA中的茴香霉素敏感性机制选择性地控制这种现象。这些发现支持了新的药理学方法的可行性，这些方法选择性地抑制可卡因相关记忆的重新巩固，以防止药物复发。
Understanding the neurobiological underpinnings of putative memory stabilization processes that maintain context-response-cocaine associations in long-term memory and underlie contextual control over addictive behavior is of great interest from an addiction treatment perspective. Using an instrumental animal model of contextual drug relapse, we show that the protein synthesis inhibitor, anisomycin, administered into the basolateral amygdala (BLA) immediately after limited (15- or 60-min) re-exposure to a previously cocaine-paired context subsequently disrupted the ability of the previously cocaine-paired context to reinstate extinguished cocaine-seeking behavior relative to vehicle. Consistent with a BLA-mediated memory reconsolidation deficit, similar impairment in cocaine-seeking behavior was not observed in “no-reactivation” control groups that received anisomycin into the BLA after (re)exposure to either a novel unpaired or an extinction-paired context nor in a neuroanatomical control group that received anisomycin into the posterior caudate-putamen, dorsally adjacent to the BLA, after re-exposure to the cocaine-paired context. Furthermore, anisomycin administered into the BLA after brief (5-min) or extensive (120-min) re-exposure to the cocaine-paired context (which was sufficient to extinguish cocaine-seeking behavior in a vehicle control group) also failed to alter responding. Together, these findings suggest that re-exposure to a cocaine-paired context in the absence of cocaine reinforcement is sufficient to trigger memory reconsolidation processes that support future drug-seeking behavior. The presence and duration of drug-related memory reactivation critically influences and anisomycin-sensitive mechanisms in the BLA selectively control this phenomenon. These findings support the feasibility of novel pharmacotherapeutic approaches that selectively inhibit the reconsolidation of cocaine-related memories in order to prevent drug relapse.
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影响因子：
3.4
作者：
Duvarci, Sevil;ben Mamou, Cyrinne;Nader, Karim
通讯作者：
Nader, Karim
影响因子：
3.4
作者：
Fuchs, RA;Tran-Nguyen, LTL;Neisewander, JL
通讯作者：
Neisewander, JL
影响因子：
3.4
作者：
EHRMAN, RN;ROBBINS, SJ;OBRIEN, CP
通讯作者：
OBRIEN, CP
影响因子：
2.7
作者：
Amaral, Olavo B.;Luft, Tatiana;Roesler, Rafael
通讯作者：
Roesler, Rafael
DOI：
10.1073/pnas.0705195104
发表时间：
2007-07-24
影响因子：
11.1
作者：
Canal, Clinton E.;Chang, Qing;Gold, Paul E.
通讯作者：
Gold, Paul E.