Halbout Briac, Hutson Collin, Agrawal Stuti, Springs Zachary A, Ostlund Sean B
Department of Anesthesiology and Perioperative Care, School of Medicine, University of California, Irvine, Irvine, CA, 92697, USA.
Department of Neurobiology and Behavior, School of Biological Sciences, University of California, Irvine, Irvine, CA, 92697, USA.
bioRxiv. 2023 Sep 15:2023.09.14.557822. doi: 10.1101/2023.09.14.557822.
Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact of spontaneous withdrawal from chronic morphine exposure on emotional, motivational, and cognitive processes involved in regulating the pursuit and consumption of natural food rewards in male rats. In Experiment 1, rats experiencing acute morphine withdrawal lost weight and displayed somatic signs of drug dependence. However, hedonically-driven sucrose consumption was significantly elevated, suggesting intact and potentially heightened emotional reward processing. In Experiment 2, rats undergoing acute morphine withdrawal displayed reduced motivation when performing an effortful response for palatable food reward. Subsequent reward devaluation testing revealed that acute withdrawal also disrupted their ability to exert flexible goal-directed control over their reward-seeking behavior. Specifically, morphine-withdrawn rats displayed insensitivity to reward devaluation both when relying on prior action-outcome learning and when given direct feedback about the consequences of their actions. In Experiment 3, rats tested after prolonged morphine withdrawal displayed heightened rather than diminished motivation for food rewards and retained their ability to engage in flexible goal-directed action selection. However, brief re-exposure to morphine was sufficient to impair motivation and disrupt goal-directed action selection, though in this case insensitivity to reward devaluation was only observed in the presence of morphine-paired context cues and in the absence of response-contingent feedback. We suggest that these opioid-withdrawal induced deficits in motivation and goal-directed control may contribute to addiction by interfering with the pursuit of adaptive alternatives to drug use.
阿片类药物成瘾是一种复发性疾病，其特征是药物使用不受控制，对通常能带来奖赏的活动兴趣降低。本研究调查了雄性大鼠从慢性吗啡暴露中自发戒断对调节天然食物奖赏的追求和消耗所涉及的情绪、动机和认知过程的影响。在实验1中，经历急性吗啡戒断的大鼠体重减轻，并表现出药物依赖的躯体症状。然而，享乐驱动的蔗糖消耗显著增加，表明情绪奖赏处理完好且可能增强。在实验2中，经历急性吗啡戒断的大鼠在为美味食物奖赏做出努力反应时表现出动机降低。随后的奖赏贬值测试表明，急性戒断也破坏了它们对奖赏寻求行为施加灵活的目标导向控制的能力。具体而言，吗啡戒断的大鼠在依赖先前的行动-结果学习以及获得关于其行动后果的直接反馈时，对奖赏贬值均表现出不敏感。在实验3中，长期吗啡戒断后接受测试的大鼠对食物奖赏的动机增强而非减弱，并保留了进行灵活的目标导向行动选择的能力。然而，短暂再次接触吗啡足以损害动机并破坏目标导向行动选择，不过在这种情况下，只有在存在与吗啡配对的情境线索且没有反应相关反馈时，才观察到对奖赏贬值不敏感。我们认为，这些阿片类药物戒断引起的动机和目标导向控制缺陷可能通过干扰对药物使用的适应性替代选择的追求而导致成瘾。
