Cellular Neurobiology Research Branch, Behavioral Neurophysiology Research Section, National Institute on Drug Abuse Intramural Research Program, 251 Bayview Blvd., Baltimore, MD, 21224, USA.
Psychopharmacology (Berl). 2013 Oct;229(3):493-501. doi: 10.1007/s00213-013-3222-6. Epub 2013 Aug 16.
Addiction is characterized by maladaptive decision-making, in which individuals seem unable to use adverse outcomes to modify their behavior. Adverse outcomes are often infrequent, delayed, and even rare events, especially when compared to the reliable rewarding drug-associated outcomes. As a result, recognizing and using information about their occurrence put a premium on the operation of so-called model-based systems of behavioral control, which allow one to mentally simulate outcomes of different courses of action based on knowledge of the underlying associative structure of the environment. This suggests that addiction may reflect, in part, drug-induced dysfunction in these systems. Here, we tested this hypothesis.
This study aimed to test whether cocaine causes deficits in model-based behavior and learning independent of requirements for response inhibition or perception of costs or punishment.
We trained rats to self-administer sucrose or cocaine for 2 weeks. Four weeks later, the rats began training on a sensory preconditioning and inferred value blocking task. Like devaluation, normal performance on this task requires representations of the underlying task structure; however, unlike devaluation, it does not require either response inhibition or adapting behavior to reflect aversive outcomes.
Rats trained to self-administer cocaine failed to show conditioned responding or blocking to the preconditioned cue. These deficits were not observed in sucrose-trained rats nor did they reflect any changes in responding to cues paired directly with reward.
These results imply that cocaine disrupts the operation of neural circuits that mediate model-based behavioral control.
成瘾的特征是适应不良的决策，个体似乎无法利用不良后果来改变他们的行为。不良后果通常是不频繁、延迟甚至罕见的事件，尤其是与可靠的、与药物相关的奖励性结果相比。因此，识别和利用有关其发生的信息需要优先考虑所谓的基于模型的行为控制系统的运作，这些系统允许人们根据对环境潜在关联结构的了解，基于不同行动过程的结果进行心理模拟。这表明，成瘾可能部分反映了这些系统在药物诱导下的功能障碍。在这里，我们检验了这一假设。
本研究旨在测试可卡因是否会导致基于模型的行为和学习出现缺陷，而无需抑制反应或感知成本或惩罚的要求。
我们训练大鼠自行摄入蔗糖或可卡因两周。四周后，大鼠开始进行感觉前条件作用和推断价值阻断任务的训练。与贬值一样，正常完成这项任务需要对底层任务结构的表示；然而，与贬值不同的是，它不需要抑制反应或适应行为来反映厌恶结果。
接受可卡因自我给药训练的大鼠未能对预先条件的线索表现出条件反应或阻断。在接受蔗糖训练的大鼠中没有观察到这些缺陷，也没有反映出对与奖励直接配对的线索的反应有任何变化。
这些结果意味着可卡因破坏了介导基于模型的行为控制的神经回路的运作。
