Neural and behavioral plasticity associated with the transition from controlled to escalated cocaine use
Neural and behavioral plasticity associated with the transition from controlled to escalated cocaine use
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DOI：
10.1016/j.biopsych.2005.04.046
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发表时间：
2005-11-01
影响因子：
10.6
通讯作者：
Robinson, TE
中科院分区：
文献类型：
--
作者：
Ferrario, CR;Gorny, G;Robinson, TE
背景：长期接触可卡因的大鼠会出现几种成瘾症状，包括药物摄入量逐渐增加，而给予有限可卡因的大鼠则不会。我们在这里询问，延长可卡因的接触是否也会产生药物诱导的敏化，这是一种与成瘾有关的神经行为可塑性形式。方法：给予大鼠有限的(1小时/次)或延长(6小时/次)的自我给药可卡因。经过一段时间的戒断后，随机抽取大鼠评估其对可卡因或灭绝期间寻求毒品的精神运动反应，并进行解剖学研究。结果：与有限获得可卡因的大鼠相比，再次接触可卡因的大鼠表现出更大的寻药行为，并对可卡因的精神运动激活作用敏感(敏化)。长期接触可卡因还与神经元上树突棘密度的增加有关，特别是在伏核核心(而不是在外壳、内侧或眼眶额叶皮质)。结论：从稳定使用可卡因到逐步使用可卡因，这是成瘾的标志。与伏隔核核心的强烈的行为敏感化和突触重组有关。
Background: Rats given extended access to cocaine develop several symptoms of addiction, including a gradual escalation of drug intake, whereas rats given limited access do not. We asked here whether extended access to cocaine also produces drug-induced sensitization, a form of neurobehavioral plasticity implicated in addiction.Methods: Rats were given limited (1 hour/session) or extended access (6 hours/session) to self-administered cocaine. Following a period of abstinence, rats were selected at random for assessment of their psychomotor response to cocaine or drug-seeking during extinction or for anatomic studies.Results: When reexposed to cocaine, rats allowed extended drug access showed greater drug-seeking behavior and were hypersensitive (sensitized) to the psychomotor activating effects of cocaine compared with rats given limited access. Extended access to cocaine was also associated with a greater increase in the density of dendritic spines on neurons specifically in the core of the nucleus accumbens (and not in the shell or medial or orbital frontal cortex).Conclusions: The transition from stable to escalated cocaine use, a hallmark of addiction.. is associated with especially robust behavioral sensitization and synaptic reorganization in the core of the nucleus accumbens.