Endocannabinoid signaling is critical for habit formation.
Endocannabinoid signaling is critical for habit formation.
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内源性大麻素信号传导对于习惯形成至关重要。
DOI：
10.3389/neuro.07.006.2007
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发表时间：
2007
影响因子：
3.5
通讯作者：
Costa, Rui M
中科院分区：
文献类型：
--
作者：
Hilario, Monica R F;Clouse, Emily;Yin, Henry H;Costa, Rui M
扩展训练可以诱导行为控制从目标导向的行为转变为习惯，目标导向的行为受行动-结果偶然性的支配，对结果预期值的变化敏感，习惯较少依赖于行动-结果关系，对结果值的变化不敏感。先前在大鼠中的研究表明，强化的间隔时间表有利于习惯的形成，而比率时间表有利于目标导向行为。然而，习性形成的分子机制还没有很好的理解。内源性大麻素可以作为通过突触前CB 1受体起作用的逆行信使，在背外侧纹状体中高度表达，背外侧纹状体是参与习惯形成的关键区域。使用可逆贬值范式，我们证实，在小鼠随机间隔时间表也有利于习惯的形成相比，随机比例时间表。我们还发现，间隔时间表的训练导致对探索新杠杆的偏好，而比率时间表的训练导致更少的泛化和更多的强化杠杆的利用。此外，携带大麻素受体I型（CB 1）杂合或纯合无效突变的小鼠表现出减少的习惯形成和增强的利用。CB 1突变小鼠的习惯形成受损不能归因于慢性发育或行为异常，因为在训练过程中特异性地阻断CB 1受体也会损害习惯形成。总之，我们的数据表明，内源性大麻素信号对习惯形成至关重要。
Extended training can induce a shift in behavioral control from goal-directed actions, which are governed by action-outcome contingencies and sensitive to changes in the expected value of the outcome, to habits which are less dependent on action-outcome relations and insensitive to changes in outcome value. Previous studies in rats have shown that interval schedules of reinforcement favor habit formation while ratio schedules favor goal-directed behavior. However, the molecular mechanisms underlying habit formation are not well understood. Endocannabinoids, which can function as retrograde messengers acting through presynaptic CB1 receptors, are highly expressed in the dorsolateral striatum, a key region involved in habit formation. Using a reversible devaluation paradigm, we confirmed that in mice random interval schedules also favor habit formation compared with random ratio schedules. We also found that training with interval schedules resulted in a preference for exploration of a novel lever, whereas training with ratio schedules resulted in less generalization and more exploitation of the reinforced lever. Furthermore, mice carrying either a heterozygous or a homozygous null mutation of the cannabinoid receptor type I (CB1) showed reduced habit formation and enhanced exploitation. The impaired habit formation in CB1 mutant mice cannot be attributed to chronic developmental or behavioral abnormalities because pharmacological blockade of CB1 receptors specifically during training also impairs habit formation. Taken together our data suggest that endocannabinoid signaling is critical for habit formation.