The rate of cocaine administration alters gene regulation and behavioral plasticity: Implications for addiction
The rate of cocaine administration alters gene regulation and behavioral plasticity: Implications for addiction
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DOI：
10.1523/jneurosci.1205-04.2004
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发表时间：
2004-07-14
影响因子：
5.3
通讯作者：
Robinson, E
中科院分区：
文献类型：
--
作者：
Samaha, AN;Mallet, N;Robinson, E
滥用药物迅速进入大脑被认为会促进成瘾，但为什么会发生这种情况尚不清楚。在本研究中，我们的特点是静脉注射可卡因（5 - 100秒）的速度的影响，认为有助于其成瘾倾向的三个效果：它的能力，以阻止多巴胺（DA）的摄取，激活立即早期基因表达，并产生精神敏化。快速输注增强可卡因阻断DA再摄取的能力，诱导c-fos和arc mRNA表达，特别是在中皮质边缘区，并产生精神敏化。因此，可卡因的递送速率既影响其神经生物学影响，也影响其诱导与成瘾有关的药物经验依赖性可塑性的能力。我们认为，快速释放的可卡因可能更容易上瘾，部分原因是这更容易诱导神经行为可塑性，导致对药物的强迫性追求。
The rapid delivery of drugs of abuse to the brain is thought to promote addiction, but why this occurs is unknown. In the present study, we characterized the influence of rate of intravenous cocaine infusion ( 5 - 100 sec) on three effects thought to contribute to its addiction liability: its ability to block dopamine (DA) uptake, to activate immediate early gene expression, and to produce psychomotor sensitization. Rapid infusions potentiated the ability of cocaine to block DA reuptake, to induce c-fos and arc mRNA expression, especially in mesocorticolimbic regions, and to produce psychomotor sensitization. Thus, the rate at which cocaine is delivered influences both its neurobiological impact and its ability to induce a form of drug experience-dependent plasticity implicated in addiction. We propose that rapidly delivered cocaine may be more addictive, in part, because this more readily induces forms of neurobehavioral plasticity that lead to the compulsive pursuit of drugs.