Kinase interest you in treating incubated cocaine-craving? A hypothetical model for treatment intervention during protracted withdrawal from cocaine.
Kinase interest you in treating incubated cocaine-craving? A hypothetical model for treatment intervention during protracted withdrawal from cocaine.
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DOI：
10.1111/gbb.12440
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Shin CB
中科院分区：
文献类型：
--
作者：
Szumlinski KK;Shin CB
作为药物成瘾的诊断标准，持续的药物渴求仍然是维持这种疾病的慢性复发性质的成瘾的最难治疗的方面。尽管精神兴奋剂成瘾的流行率很高，但目前还没有FDA批准的药物用于减少渴望。在很大程度上，这反映了我们对药物渴求的神经生物学基础缺乏了解。在人类中，线索引发的药物渴求与前额叶皮层区域的过度兴奋有关。啮齿类动物可卡因成瘾模型表明，过量服用可卡因的历史会影响前额叶皮层内的兴奋性谷氨酸信号，从而在长期戒断期间驱动药物寻求行为。这篇综述总结了可卡因相关线索的能力，以增加高度药物经验丰富的大鼠的渴望与前边缘皮层内谷氨酸释放的戒断依赖性孵育的证据。我们讨论了mGlu 1/5受体的刺激如何增加经典和非经典细胞内信号通路的激活状态，并提出了一个理论分子模型，其中激活的几个激酶效应器，包括蛋白激酶C，细胞外信号调节激酶和磷酸肌醇3-激酶（PI 3 K）可能导致受体脱敏占持久的可卡因渴望在长期戒断。最后，这篇评论讨论了现有的，FDA批准的，靶向激酶功能的药物作为一种新的方法来干预可卡因成瘾的渴望的潜力。
A diagnostic criterion for drug addiction, persistent drug-craving continues to be the most treatment-resistant aspect of addiction that maintains the chronic, relapsing, nature of this disease. Despite the high prevalence of psychomotor stimulant addiction, there currently exists no FDA-approved medication for craving reduction. In good part, this reflects our lack of understanding of the neurobiological underpinnings of drug-craving. In humans, cue-elicited drug-craving is associated with the hyperexcitability of prefrontal cortical regions. Rodent models of cocaine addiction indicate that a history of excessive cocaine-taking impacts excitatory glutamate signaling within the prefrontal cortex to drive drug-seeking behavior during protracted withdrawal. This review summarizes evidence that the capacity of cocaine-associated cues to augment craving in highly drug-experienced rats relates to a withdrawal-dependent incubation of glutamate release within prelimbic cortex. We discuss how stimulation of mGlu1/5 receptors increases the activational state of both canonical and noncanonical intracellular signaling pathways and present a theoretical molecular model in which the activation of several kinase effectors, including protein kinase C, extracellular signal-regulated kinase and phosphoinositide 3-kinase (PI3K) might lead to receptor desensitization to account for persistent cocaine-craving during protracted withdrawal. Finally, this review discusses the potential for existing, FDA-approved, pharmacotherapeutic agents that target kinase function as a novel approach to craving intervention in cocaine addiction.
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DOI：
10.1523/jneurosci.1914-12.2012
发表时间：
2012-08-22
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fanous S;Goldart EM;Theberge FR;Bossert JM;Shaham Y;Hope BT
通讯作者：
Hope BT
影响因子：
5.4
作者：
Aoyama, K.;Barnes, J.;Grimm, J. W.
通讯作者：
Grimm, J. W.
影响因子：
3.4
作者：
Adhikary S;Caprioli D;Venniro M;Kallenberger P;Shaham Y;Bossert JM
通讯作者：
Bossert JM
影响因子：
2.3
作者：
Ben-Shahar, Osnat;Obara, Ilona;Ary, Alexis W.;Ma, Natalie;Mangiardi, Mario A.;Medina, Robert L.;Szumlinski, Karen K.
通讯作者：
Szumlinski, Karen K.
影响因子：
16.2
作者：
Gereau, RW;Heinemann, SF
通讯作者：
Heinemann, SF