Locomotor Sensitization to Ethanol Impairs NMDA Receptor-Dependent Synaptic Plasticity in the Nucleus Accumbens and Increases Ethanol Self-Administration
Locomotor Sensitization to Ethanol Impairs NMDA Receptor-Dependent Synaptic Plasticity in the Nucleus Accumbens and Increases Ethanol Self-Administration
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DOI：
10.1523/jneurosci.5839-11.2013
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发表时间：
2013-03-13
影响因子：
5.3
通讯作者：
Weiner, Jeffrey L.
中科院分区：
文献类型：
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作者：
Abrahao, Karina Possa;Ariwodola, Olusegun J.;Weiner, Jeffrey L.
虽然酗酒是一个世界性的问题，导致数百万人死亡，但只有一小部分酒精使用者上瘾。具体的神经基板负责个体差异的脆弱性酒精成瘾是未知的。在这项研究中，我们使用啮齿动物模型来研究与乙醇自发致敏发展中的个体差异相关的行为和突触相关性，这是一种与成瘾脆弱性相关的药物依赖性行为可塑性。雄性Swiss韦伯斯特小鼠每天用生理盐水或1.8 g/kg乙醇处理21 d。运动活性测试每周进行一次，每次15分钟后立即注射生理盐水或乙醇。在至少11天的撤退后，盐水或乙醇处理的小鼠的队列被用来表征运动敏化，乙醇饮用，并在延髓核的神经元能突触传递之间的关系。乙醇处理的小鼠，表达运动敏感的乙醇喝了显着更多的乙醇比盐水处理的科目和乙醇处理的动物弹性这种形式的行为可塑性。此外，乙醇致敏的小鼠也有减少的延髓NMDA受体的功能和表达，以及赤字的NMDA受体依赖性长期抑郁症在延髓核的核心后，长期戒断。这些研究结果表明，中断的突触核NMDA受体依赖的可塑性可能代表与乙醇诱导的运动敏感化和增加的倾向，消耗乙醇的突触相关。
Although alcoholism is a worldwide problem resulting in millions of deaths, only a small percentage of alcohol users become addicted. The specific neural substrates responsible for individual differences in vulnerability to alcohol addiction are not known. In this study, we used rodent models to study behavioral and synaptic correlates related to individual differences in the development of ethanol locomotor sensitization, a form of drug-dependent behavioral plasticity associated with addiction vulnerability. Male Swiss Webster mice were treated daily with saline or 1.8 g/kg ethanol for 21 d. Locomotor activity tests were performed once a week for 15 min immediately after saline or ethanol injections. After at least 11 d of withdrawal, cohorts of saline-or ethanol-treated mice were used to characterize the relationships between locomotor sensitization, ethanol drinking, and glutamatergic synaptic transmission in the nucleus accumbens. Ethanol-treated mice that expressed locomotor sensitization to ethanol drank significantly more ethanol than saline-treated subjects and ethanol-treated animals resilient to this form of behavioral plasticity. Moreover, ethanol-sensitized mice also had reduced accumbal NMDA receptor function and expression, as well as deficits in NMDA receptor-dependent long-term depression in the nucleus accumbens core after a protracted withdrawal. These findings suggest that disruption of accumbal core NMDA receptor-dependent plasticity may represent a synaptic correlate associated with ethanol-induced locomotor sensitization and increased propensity to consume ethanol.