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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Cocaine-induced potentiation of synaptic strength in dopamine neurons: Behavioral correlates in GluRA(-/-) mice
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Cocaine-induced potentiation of synaptic strength in dopamine neurons: Behavioral correlates in GluRA(-/-) mice

机译：可卡因诱导多巴胺神经元突触强度的增强：GluRA（-/-）小鼠中的行为相关。

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Synaptic plasticity in the mesolimbic dopamine (DA) system is thought to contribute to the neural adaptations that mediate behavioral sensitization, a model for core aspects of addiction. Recently, it has been demonstrated that multiple classes of drugs of abuse, as well as acute stress, enhance strength at excitatory synapses on midbrain DA neurons. Here, we show that both the cocaine- and stress-induced synaptic enhancement involves an up-regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. This enhancement requires the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluRA as evidenced by its absence in mice lacking this subunit. The cocaine-elicited, but not the stress-elicited, synaptic potentiation in DA neurons was blocked by a D1-like receptor antagonist, indicating that the in vivo triggering mechanisms differ for these forms of experience-dependent synaptic modification. Surprisingly, behavioral sensitization to cocaine was elicited in GluRA(-/-) mice, indicating that potentiation of excitatory synaptic transmission in DA neurons is not necessary for this form of behavioral plasticity. However, GluRA(-/-) mice did not exhibit a conditioned locomotor response when placed in a context previously paired with cocaine, nor did they exhibit conditioned place preference in response to cocaine. We suggest that the drug-induced enhancement of excitatory synaptic transmission in midbrain DA neurons, although not required for behavioral sensitization per se, may contribute to the attribution of incentive value to drug-associated cues.
机译：中脑边缘多巴胺（DA）系统中的突触可塑性被认为有助于介导行为敏化的神经适应，这是成瘾的核心方面的模型。最近，已经证明，多种滥用药物以及急性应激会增强中脑DA神经元的兴奋性突触强度。在这里，我们表明可卡因和应激诱导的突触增强均涉及α-氨基-3-羟基-5-甲基-5-甲基-4-异恶唑丙酸受体的上调。这种增强需要α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体亚基GluRA，这在缺乏该亚基的小鼠中不存在。 D1样受体拮抗剂阻断了可卡因引起的但不是应激引起的DA神经元突触增强，这表明这些形式的经验依赖性突触修饰的体内触发机制不同。出乎意料的是，在GluRA（-/-）小鼠中引起了对可卡因的行为敏化，表明DA神经元中兴奋性突触传递的增强对于这种形式的行为可塑性不是必需的。但是，将GluRA（-/-）小鼠放在先前与可卡因配对的环境中时，它不会表现出自发的运动反应，也不会表现出对可卡因的反应所产生的条件性位置偏好。我们建议，尽管中枢行为本身并不要求药物引起中脑DA神经元兴奋性突触传递的增强，但可能有助于将激励价值归因于与药物相关的提示。

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