Department of Psychiatry, Yale University, New Haven, Connecticut.
Department of Neuroscience, Yale University, New Haven, Connecticut.
Biol Psychiatry. 2019 Jun 1;85(11):936-945. doi: 10.1016/j.biopsych.2018.12.017. Epub 2019 Jan 4.
Disruptions in the decision-making processes that guide action selection are a core feature of many psychiatric disorders, including addiction. Decision making is influenced by the goal-directed and habitual systems that can be computationally characterized using model-based and model-free reinforcement learning algorithms, respectively. Recent evidence suggests an imbalance in the influence of these reinforcement learning systems on behavior in individuals with substance dependence, but it is unknown whether these disruptions are a manifestation of chronic drug use and/or are a preexisting risk factor for addiction.
We trained adult male rats on a multistage decision-making task to quantify model-free and model-based processes before and after self-administration of methamphetamine or saline.
Individual differences in model-free, but not model-based, learning prior to any drug use predicted subsequent methamphetamine self-administration; rats with lower model-free behavior took more methamphetamine than rats with higher model-free behavior. This relationship was selective to model-free updating following a rewarded, but not unrewarded, choice. Both model-free and model-based learning were reduced in rats following methamphetamine self-administration, which was due to a decrement in the ability of rats to use unrewarded outcomes appropriately. Moreover, the magnitude of drug-induced disruptions in model-free learning was not correlated with disruptions in model-based behavior, indicating that drug self-administration independently altered both reinforcement learning strategies.
These findings provide direct evidence that model-free and model-based learning mechanisms are involved in select aspects of addiction vulnerability and pathology, and they provide a unique behavioral platform for conducting systems-level analyses of decision making in preclinical models of mental illness.
指导行动选择的决策过程的中断是许多精神疾病的核心特征,包括成瘾。决策受到目标导向和习惯系统的影响,可以使用基于模型和无模型强化学习算法分别对其进行计算描述。最近的证据表明,在物质依赖个体中,这些强化学习系统对行为的影响存在不平衡,但尚不清楚这些中断是慢性药物使用的表现还是成瘾的先前风险因素。
我们在多阶段决策任务中对成年雄性大鼠进行训练,以在进行 methamphetamine 或盐水自我给药之前和之后量化无模型和基于模型的过程。
在任何药物使用之前,个体在无模型学习方面的差异,但不是基于模型的学习,预测了随后的 methamphetamine 自我给药;无模型行为较低的大鼠比无模型行为较高的大鼠摄入更多的 methamphetamine。这种关系是选择性的,仅适用于在获得奖励但未获得奖励的选择后进行的无模型更新。在 methamphetamine 自我给药后,大鼠的无模型和基于模型的学习都减少了,这是由于大鼠适当使用无奖励结果的能力下降所致。此外,药物引起的无模型学习中断的程度与基于模型的行为中断无关,表明药物自我给药独立地改变了两种强化学习策略。
这些发现提供了直接证据,表明无模型和基于模型的学习机制参与了成瘾易感性和病理的某些方面,并且它们为在精神疾病的临床前模型中进行决策的系统水平分析提供了独特的行为平台。