Cue-induced reinstatement of alcohol-seeking behavior is associated with increased CaMKII T286 phosphorylation in the reward pathway of mice.
Cue-induced reinstatement of alcohol-seeking behavior is associated with increased CaMKII T286 phosphorylation in the reward pathway of mice.
复制标题
提示引起的寻求酒精行为的恢复与小鼠奖励途径中CAMKII T286磷酸化的增加有关。
DOI：
10.1016/j.pbb.2017.10.011
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Hodge CW
中科院分区：
文献类型：
--
作者：
Salling MC;Hodge CJ;Psilos KE;Eastman VR;Faccidomo SP;Hodge CW
线索诱导的寻求酒精行为的恢复是成瘾的标志性行为病理。有证据表明，复原性(例如，复发)可能由神经可塑性基础上的细胞信号系统调节。许多可塑性事件都需要激活奖赏通路中的钙钙调素依赖的蛋白激酶II(CaMKII)，如伏隔核和杏仁核。我们试图确定线索诱导的寻酒行为的恢复是否与CaMKII-T286的激活状态(例如，磷酸化)的变化有关。对雄性C57BL/6J小鼠(n=14)进行杠杆挤压训练，按固定比例4的程序添加甜酒(2%蔗糖+9%乙醇)。在消亡14天(没有线索或增强剂)后，小鼠经历了反应条件恢复(n=7)和额外消亡一天(n=7)。实验结束后立即取出脑组织，进行pCaMKII-T286免疫反应(IR)检测。用BioQuant图像分析软件对脑冠状切片中pCaMKII-T286阳性细胞数进行定量。在整个基线阶段，小鼠对酒精的反应明显多于对不活跃水平的反应，平均酒精摄入量为1.1±0.03g/kg/1小时。在消退过程中，到第7天，对酒精水平的反应下降到非活跃水平。在一次测试中，观察到明显的线索诱导的酒精寻找的恢复，而对非活跃水平没有影响。与消退对照组相比，恢复与杏仁核(LA和BLA)、伏隔核(AcbSh)、外侧隔核、背内侧丘脑和梨状皮质的pCaMKII-T286 IR增加有关。无变化的脑区包括背侧纹状体、内侧隔、扣带皮质、缰核、室旁丘脑和腹侧下丘脑。这些结果表明，反应条件线索诱导的酒精寻找行为的恢复与雄性C57BL/6J小鼠特定的奖赏和记忆相关脑区pCaMKII-T286的选择性增加有关。联想学习和记忆的主要分子机制可能调节酒精成瘾的复发。
Cue-induced reinstatement of alcohol-seeking is a hallmark behavioral pathology of addiction. Evidence suggests that reinstatement (e.g., relapse), may be regulated by cell signaling systems that underlie neuroplasticity. A variety of plasticity events require activation of calcium calmodulin-dependent protein kinase II (CaMKII) in components of the reward pathway, such as the nucleus accumbens and amygdala. We sought to determine if cue-induced reinstatement of alcohol-seeking behavior is associated with changes in the activation state (e.g., phosphorylation) of CaMKII-T286. Male C57BL/6J mice (n = 14) were trained to lever press on a fixed-ratio-4 schedule of sweetened alcohol (2% sucrose + 9% EtOH) reinforcement. After 14-d of extinction (no cues or reinforcers), mice underwent a response-contingent reinstatement (n = 7) vs. an additional day of extinction (n = 7). Brains were removed immediately after the test and processed for evaluation of pCaMKII-T286 immunoreactivity (IR). Number of pCaMKII-T286 positive cells/mm2 was quantified from coronal brain sections using Bioquant Image Analysis software. Mice emitted significantly more responses on the alcohol vs. the inactive lever throughout the baseline phase with average alcohol intake of 1.1 ± 0.03 g/kg/1-h. During extinction, responses on the alcohol lever decreased to inactive lever levels by day 7. Significant cue-induced reinstatement of alcohol-seeking was observed during a single test with no effects on the inactive lever. Reinstatement was associated with increased pCaMKII-T286 IR specifically in amygdala (LA and BLA), nucleus accumbens (AcbSh), lateral septum, mediodorsal thalamus, and piriform cortex as compared to extinction control. Brain regions showing no change included the dorsal striatum, medial septum, cingulate cortex, habenula, paraventricular thalamus, and ventral hypothalamus. These results show response contingent cue-induced reinstatement of alcohol-seeking behavior is associated with selective increases in pCaMKII-T286 in specific reward- and memory-related brain regions of male C57BL/6J mice. Primary molecular mechanisms of associative learning and memory may regulate relapse in alcohol addiction.
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影响因子：
3.4
作者：
Cannady R;Fisher KR;Durant B;Besheer J;Hodge CW
通讯作者：
Hodge CW
DOI：
10.1111/j.1460-9568.2008.06517.x
发表时间：
2008-12
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Chaudhri N;Sahuque LL;Cone JJ;Janak PH
通讯作者：
Janak PH
DOI：
10.1523/jneurosci.2827-10.2010
发表时间：
2010-12-01
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Briand LA;Vassoler FM;Pierce RC;Valentino RJ;Blendy JA
通讯作者：
Blendy JA
影响因子：
3.4
作者：
Cannady R;Fisher KR;Graham C;Crayle J;Besheer J;Hodge CW
通讯作者：
Hodge CW
影响因子：
3.3
作者：
Funk, D;Li, Z;Lê, AD
通讯作者：
Lê, AD