Incubation of Cocaine Seeking following Brief Cocaine Experience in Mice Is Enhanced by mGluR1 Blockade
Incubation of Cocaine Seeking following Brief Cocaine Experience in Mice Is Enhanced by mGluR1 Blockade
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DOI：
10.1523/jneurosci.1076-13.2014
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发表时间：
2014-01-29
影响因子：
5.3
通讯作者：
Spanagel, Rainer
中科院分区：
文献类型：
--
作者：
Halbout, Briac;Bernardi, Rick E.;Spanagel, Rainer
可卡因渴望的孵化描述了从长期可卡因自我管理的撤退过程中的线索诱导的可卡因寻求的时间依赖性增强，并需要在神经可塑性的时间依赖性变化的水平上的神经元突触的核内（NAc）。与大多数使用多次可卡因线索条件反射的研究相反，本研究测试了可卡因经验有限的小鼠（即，一个单一的条件反射会话）的线索介导的可卡因寻求及其相关的变化，在谷氨酸系统的孵化。与自我给予盐水的小鼠相比，在单次会议期间自我给予可卡因的小鼠表现出对药物相关线索的反应的时间依赖性增加。这种行为与AMPA和NMDA受体结合特征的变化有关。此外，第一组代谢型谷氨酸受体（mGluR1）mRNA水平在几个脑区，包括NAc改变。由于mGluR1在可卡因诱导的可塑性控制中的关键作用，我们研究了mGluR1在药物线索介导的可卡因寻找形成中的作用。在长时间戒断后，与溶剂处理的小鼠相比，在可卡因自我给药后给予mGluR1拮抗剂的小鼠显示出增加的可卡因寻求。这些结果表明，有限的可卡因经验足以诱导神经生物学的变化，使最初的中性线索，以获得动机的价值，随着时间的推移，这种影响可能涉及谷氨酸信号通过mGluR1。
The incubation of cocaine craving describes the time-dependent augmentation of cue-induced cocaine seeking during withdrawal from prolonged cocaine self-administration and requires time-dependent changes in neuroplasticity at the level of glutamatergic synapses in the nucleus accumbens (NAc). In contrast to most studies that use multiple cocaine-cue conditioning sessions, the present study tested mice with limited cocaine experience (i.e., a single conditioning session) in the incubation of cue-mediated cocaine seeking and its associated changes in the glutamate system. Mice that self-administered cocaine during a single session exhibited a time-dependent increase in their response for the drug-associated cue as compared to mice that self-administered saline. This behavior was associated with changes in AMPA and NMDA receptor binding characteristics. Furthermore, Group I metabotropic glutamate receptor (mGluR1) mRNA levels were altered in several brain regions, including the NAc. Because of the pivotal role of mGluR1 in the control of cocaine-induced plasticity, we investigated the role of mGluR1 in the formation of drug cue-mediated cocaine seeking. After prolonged withdrawal, mice in which an mGluR1 antagonist was administered following cocaine self-administration displayed increased cocaine seeking compared to vehicle-treated mice. These results suggest that limited cocaine experience is sufficient to induce neurobiological changes that enable an initially neutral cue to acquire motivational value that increases over time, an effect that likely involves glutamate signaling through mGluR1.