Biopsychology Department, 530 Church Street, East Hall, University of Michigan, Ann Arbor, MI 48109, USA.
Curr Biol. 2013 Feb 18;23(4):282-9. doi: 10.1016/j.cub.2013.01.016. Epub 2013 Jan 31.
Learned cues for pleasant reward often elicit desire, which, in addicts, may become compulsive. According to the dominant view in addiction neuroscience and reinforcement modeling, such desires are the simple products of learning, coming from a past association with reward outcome.
We demonstrate that cravings are more than merely the products of accumulated pleasure memories-even a repulsive learned cue for unpleasantness can become suddenly desired via the activation of mesocorticolimbic circuitry. Rats learned repulsion toward a Pavlovian cue (a briefly-inserted metal lever) that always predicted an unpleasant Dead Sea saltiness sensation. Yet, upon first reencounter in a novel sodium-depletion state to promote mesocorticolimbic reactivity (reflected by elevated Fos activation in ventral tegmentum, nucleus accumbens, ventral pallidum, and the orbitofrontal prefrontal cortex), the learned cue was instantly transformed into an attractive and powerful motivational magnet. Rats jumped and gnawed on the suddenly attractive Pavlovian lever cue, despite never having tasted intense saltiness as anything other than disgusting.
Instant desire transformation of a learned cue contradicts views that Pavlovian desires are essentially based on previously learned values (e.g., prediction error or temporal difference models). Instead desire is recomputed at reencounter by integrating Pavlovian information with the current brain/physiological state. This powerful brain transformation reverses strong learned revulsion into avid attraction. When applied to addiction, related mesocorticolimbic transformations (e.g., drugs or neural sensitization) of cues for already-pleasant drug experiences could create even more intense cravings. This cue/state transformation helps define what it means to say that addiction hijacks brain limbic circuits of natural reward.
学习愉悦奖励的线索通常会引起欲望，而对于成瘾者来说，这种欲望可能会变得强迫性。根据成瘾神经科学和强化模型的主流观点，这种欲望只是学习的简单产物，源于与奖励结果的过去关联。
我们证明，渴望不仅仅是积累的愉悦记忆的产物——即使是一个令人不快的习得线索，也可以通过激活中脑边缘回路而突然变得渴望。老鼠学会了对一个条件反射线索（一个短暂插入的金属杠杆）产生厌恶，这个线索总是预示着一种不愉快的死海咸味感觉。然而，当它们在一种新的钠耗竭状态下首次重新遇到这种线索时，这种线索会突然变得有吸引力，从而促进中脑边缘回路的反应性（表现为腹侧被盖区、伏隔核、腹侧苍白球和眶额前额皮层中的 Fos 激活增加）。学会的线索瞬间变成了一个有吸引力和强大的动机磁铁。老鼠会跳起来啃咬突然变得有吸引力的条件反射杠杆线索，尽管它们从未将强烈的咸味体验为任何令人愉悦的东西。
习得线索的即时欲望转变与认为条件反射欲望本质上基于先前学习的价值（例如，预测误差或时间差异模型）的观点相矛盾。相反，欲望是在重新遇到时通过将条件反射信息与当前的大脑/生理状态相结合重新计算的。这种强大的大脑转变将强烈的习得厌恶转变为强烈的吸引力。当应用于成瘾时，与中脑边缘回路相关的类似变化（例如，药物或神经敏化）可能会导致对已经愉悦的药物体验的线索产生更强烈的渴望。这种线索/状态的转变有助于定义成瘾劫持大脑边缘回路的自然奖励的含义。
