Basolateral amygdala corticotropin-releasing factor receptor type 1 regulates context-cocaine memory strength during reconsolidation in a sex-dependent manner.
Basolateral amygdala corticotropin-releasing factor receptor type 1 regulates context-cocaine memory strength during reconsolidation in a sex-dependent manner.
复制标题
DOI：
10.1016/j.neuropharm.2021.108819
复制
发表时间：
2021-12-01
影响因子：
4.7
通讯作者：
Fuchs RA
中科院分区：
文献类型：
--
作者：
Ritchie JL;Walters JL;Galliou JMC;Christian RJ;Qi S;Savenkova MI;Ibarra CK;Grogan SR;Fuchs RA
基底外侧杏仁核（BLA）是可卡因记忆再巩固的关键脑区。促肾上腺皮质激素释放因子受体1型（CRFR1）在BLA中密集表达，刺激CRFR1可激活介导记忆再巩固的细胞内信号级联反应。因此，我们验证了BLA CRFR1刺激对于可卡因记忆再巩固是必要和充分的假设。利用药物复发的工具模型，雄性和雌性Sprague-Dawley大鼠在不同的环境背景下接受10天的可卡因自我给药训练，然后在不同的环境下进行7天的灭绝训练。接下来，将大鼠再次暴露在可卡因配对的环境中15分钟，以启动可卡因记忆检索和不稳定。立即或6小时后，大鼠接受双侧体、抗塔拉明（CRFR1拮抗剂；500 ng/半球）或促肾上腺皮质激素释放因子（CRF； 0.2、30或500 ng/半球）输注到BLA。三天后评估药物情境诱导的可卡因寻求的变化（情境-可卡因记忆强度指数）。雌性大鼠比雄性大鼠自我注射更多的可卡因，并表现出更多的灭绝反应。在记忆提取后立即（即当可卡因记忆不稳定时），而不是6小时后（即在记忆再巩固后），bla内安他拉明治疗，相对于交通工具，在独立于性别的测试中减弱了药物情境诱导的可卡因寻求。相反，在女性中，bla内CRF治疗选择性地增加了这种行为，呈u型剂量依赖性。在对照实验中，高剂量（行为无效）的CRF治疗并没有降低女性BLA CRFR1细胞表面的表达。因此，BLA CRFR1信号是必要和充分的，以性别依赖的方式调节可卡因记忆强度。
The basolateral amygdala (BLA) is a critical brain region for cocaine-memory reconsolidation. Corticotropin-releasing factor receptor type 1 (CRFR1) is densely expressed in the BLA, and CRFR1 stimulation can activate intra-cellular signaling cascades that mediate memory reconsolidation. Hence, we tested the hypothesis that BLA CRFR1 stimulation is necessary and sufficient for cocaine-memory reconsolidation. Using an instrumental model of drug relapse, male and female Sprague-Dawley rats received cocaine self-administration training in a distinct environmental context over 10 days followed by extinction training in a different context over 7 days. Next, rats were re-exposed to the cocaine-paired context for 15 min to initiate cocaine-memory retrieval and destabilization. Immediately or 6 h after this session, the rats received bilateral vehicle, antalarmin (CRFR1 antagonist; 500 ng/hemisphere), or corticotropin-releasing factor (CRF; 0.2, 30 or 500 ng/hemisphere) infusions into the BLA. Resulting changes in drug context-induced cocaine seeking (index of context-cocaine memory strength) were assessed three days later. Female rats self-administered more cocaine infusions and exhibited more extinction responding than males. Intra-BLA antalarmin treatment immediately after memory retrieval (i.e., when cocaine memories were labile), but not 6 h later (i.e., after memory reconsolidation), attenuated drug context-induced cocaine seeking at test independent of sex, relative to vehicle. Conversely, intra-BLA CRF treatment increased this behavior selectively in females, in a U-shaped dose-dependent fashion. In control experiments, a high (behaviorally ineffective) dose of CRF treatment did not reduce BLA CRFR1 cell-surface expression in females. Thus, BLA CRFR1 signaling is necessary and sufficient, in a sex-dependent manner, for regulating cocaine-memory strength.
登录
查看更多内容
DOI：
10.1523/jneurosci.1393-11.2011
发表时间：
2011-08-03
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Blacktop JM;Seubert C;Baker DA;Ferda N;Lee G;Graf EN;Mantsch JR
通讯作者：
Mantsch JR
影响因子：
3.4
作者：
Arguello, Amy A.;Hodges, Matthew A.;Wells, Audrey M.;Lara, Honorio, III;Xie, Xiaohu;Fuchs, Rita A.
通讯作者：
Fuchs, Rita A.
影响因子：
3.4
作者：
Boyson, Christopher O.;Miguel, Tarciso T.;Quadros, Isabel M.;DeBold, Joseph F.;Miczek, Klaus A.
通讯作者：
Miczek, Klaus A.
影响因子：
56.9
作者：
Eisenberg, M;Kobilo, T;Dudai, Y
通讯作者：
Dudai, Y
影响因子：
7.4
作者：
Coric, Vladimir;Feldman, Howard H.;Stock, Elyse G.
通讯作者：
Stock, Elyse G.