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首页> 外文期刊>Science Signaling >beta-Arrestin-biased beta-adrenergic signaling promotes extinction learning of cocaine reward memory
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beta-Arrestin-biased beta-adrenergic signaling promotes extinction learning of cocaine reward memory

机译：β-诱导偏见的β-肾上腺素能信号促进CoCaine奖励记忆的消失学习

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摘要

Extinction learning of cocaine-associated contextual cues can help prevent cocaine addicts from relapsing. Pharmacological manipulation of beta-adrenergic receptor (beta-AR) during extinction learning is being developed as a potential strategy to treat drug addiction. We demonstrated that the extinction learning of cocaine-associated memory was mediated by beta-arrestin2-biased but not heterotrimeric guanine nucleotide-binding protein (G protein)-dependent beta-adrenergic signaling. We found that administration of the nonbiased beta-AR antagonist propranolol, but not the G protein-biased beta-AR antagonist carvedilol, blocked extinction learning of cocaine-conditioned place preference and the associated ERK activation in the infralimbic prefrontal cortex. Overexpression of beta-arrestin2 in the infralimbic prefrontal cortex promoted extinction learning, which was blocked by propranolol. Knockout of beta-arrestin2 in the infralimbic prefrontal cortex, specifically in excitatory neurons, impaired extinction learning of cocaine-conditioned place preference, which was not rescued by carvedilol. beta-Arrestin2 signaling in infralimbic excitatory neurons was also required for the extinction learning in the cocaine self-administration model. Our results suggest that beta-arrestin-biased beta-adrenergic signaling in the infralimbic prefrontal cortex regulates extinction learning of cocaine-associated memories and could be therapeutically targeted to treat addiction.
机译：Cocaine相关的上下文提示的灭绝学习可以帮助防止可卡因上瘾复发。在消灭学习期间β-肾上腺素能受体（Beta-AR）的药理操纵正在制定为治疗吸毒成瘾的潜在策略。我们证明了可卡因相关内存的消灭学习是通过β-arretIn2-偏置的，但不是异络鸟嘌呤核苷酸结合蛋白（G蛋白） - 依赖性β-肾上腺素能信号传导。我们发现施用非偏见的β-AR拮抗剂丙醇醇，但不是G蛋白质偏置的β-AR拮抗剂Carvedilol，阻断了可卡因条件的偏爱的消灭学习，并且在内部额外皮层中的相关ERK活化。 β-interir infraltmbic预甲状腺皮质中的抑制过度表达促进了消化学习，其被普萘洛尔阻断。在兴奋性神经元中的Infralimbic Preferal Cortex中敲除β-Arcredin2，特别是在兴奋性神经元中，消除可卡因条件偏好的消灭学习，这不会被卡维地洛救出。在可卡因自我给药模型中，灭绝学习也需要β-interniN2在InfraMbic兴奋神经元中的信号传导。我们的研究结果表明，Infralimbic Preforal Cortex中的β-Arction型β-肾上腺素能信号调节了可卡因相关记忆的消灭学习，并且可以治疗靶向治疗成瘾。

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