Lu Lin, Koya Eisuke, Zhai Haifeng, Hope Bruce T, Shaham Yavin
Department of Neuropharmacology, National Institute on Drug Dependence, Peking University, Beijing 100083, China.
Trends Neurosci. 2006 Dec;29(12):695-703. doi: 10.1016/j.tins.2006.10.005. Epub 2006 Nov 7.
Cocaine addiction is characterized by compulsive drug-taking behavior and high rates of relapse. According to recent theories, this addiction is due to drug-induced adaptations in the cellular mechanisms that underlie normal learning and memory. Such mechanisms involve signaling by extracellular signal-regulated kinase (ERK). As we review here, evidence from rodent studies also implicates ERK in cocaine psychomotor sensitization, cocaine reward, consolidation and reconsolidation of memories for cocaine cues, and time-dependent increases in cocaine seeking after withdrawal (incubation of cocaine craving). The role of ERK in these behaviors involves long-term stable alterations in synaptic plasticity that result from repeated cocaine exposure, and also rapidly induced alterations in synaptic transmission events that acutely control cocaine-seeking behaviors. Pharmacological manipulations that decrease the extent to which cocaine and cocaine cues induce ERK activity might therefore be considered as potential treatments for cocaine addiction.
可卡因成瘾的特征是强迫性吸毒行为和高复发率。根据最近的理论,这种成瘾是由于药物诱导的正常学习和记忆所依赖的细胞机制发生了适应性变化。此类机制涉及细胞外信号调节激酶(ERK)的信号传导。正如我们在此所综述的,来自啮齿动物研究的证据也表明,ERK与可卡因精神运动性敏感化、可卡因奖赏、可卡因线索记忆的巩固和再巩固,以及戒断后可卡因觅求行为随时间的增加(可卡因渴求的潜伏期)有关。ERK在这些行为中的作用涉及反复接触可卡因导致的突触可塑性的长期稳定改变,以及急性控制可卡因觅求行为的突触传递事件的快速诱导改变。因此,降低可卡因和可卡因线索诱导ERK活性程度的药理学操作可能被视为可卡因成瘾的潜在治疗方法。