Integrative Neuroscience Section, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland 21224, USA.
J Neurosci. 2010 Nov 17;30(46):15457-63. doi: 10.1523/JNEUROSCI.4072-10.2010.
The development of drug-seeking habits is implicated in the transition from recreational drug use to addiction. Using a drug seeking/taking chained schedule of intravenous cocaine self-administration and reward devaluation methods in rats, the present studies examined whether drug seeking that is initially goal-directed becomes habitual after prolonged drug seeking and taking. Devaluation of the outcome of the drug seeking link (i.e., the drug taking link of the chained schedule) by extinction significantly decreased drug seeking indicating that behavior is goal-directed rather than habitual. With, however, more prolonged drug experience, animals transitioned to habitual cocaine seeking. Thus, in these animals, cocaine seeking was insensitive to outcome devaluation. Moreover, when the dorsolateral striatum, an area implicated in habit learning, was transiently inactivated, outcome devaluation was effective in decreasing drug seeking indicating that responding was no longer habitual but had reverted to control by the goal-directed system. These studies provide direct evidence that cocaine seeking becomes habitual with prolonged drug experience and describe a rodent model with which to study the neural mechanisms underlying the transition from goal-directed to habitual drug seeking.
药物寻求习惯的发展与从娱乐性药物使用向成瘾的转变有关。本研究采用药物寻求/摄取静脉内可卡因自我给药和奖励贬值方法在大鼠中，研究了在长时间的药物寻求和摄取后，最初目标导向的药物寻求是否会变得习惯性。通过消除（即连锁时间表的药物摄取链接）对药物寻求链接的结果进行贬值，显著降低了药物寻求，表明行为是目标导向的而不是习惯性的。然而，随着药物经验的延长，动物过渡到习惯性可卡因寻求。因此，在这些动物中，可卡因寻求对结果贬值不敏感。此外，当背外侧纹状体（与习惯学习有关的区域）短暂失活时，结果贬值有效降低了药物寻求，表明反应不再是习惯性的，而是通过目标导向系统恢复了控制。这些研究提供了直接证据，表明随着药物经验的延长，可卡因寻求变得习惯性，并描述了一种啮齿动物模型，用于研究从目标导向到习惯性药物寻求的神经机制。
