Department of Anesthesiology and Perioperative Care, School of Medicine, University of California, Irvine, Irvine, California, USA.
Department of Neurobiology and Behavior, School of Biological Sciences, University of California, Irvine, Irvine, California, USA.
Addict Biol. 2024 May;29(5):e13393. doi: 10.1111/adb.13393.
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 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 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 disrupted their ability to exert flexible goal-directed control over reward seeking. Specifically, morphine-withdrawn rats were impaired in using current reward value to select actions both when relying on prior action-outcome learning and when given direct feedback about the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, rats were only impaired in using reward value to select actions 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,其特征是无法控制地使用药物和对正常有奖励作用的活动的兴趣降低。本研究调查了慢性吗啡暴露后自发戒断对雄性大鼠调节食物奖励追求和消费的情绪、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,快感驱动的蔗糖消耗显著增加,表明完整且潜在增强的奖励处理。在实验 2 中,经历急性吗啡戒断的大鼠在进行费力的美味食物奖励反应时表现出动机降低。随后的奖励贬值测试表明,急性戒断破坏了他们对奖励寻求进行灵活目标导向控制的能力。具体来说,吗啡戒断大鼠在依赖先前的行为-结果学习和在获得关于其行为后果的直接反馈时,都无法利用当前奖励价值来选择行为。在实验 3 中,经过长时间吗啡戒断测试的大鼠表现出对食物奖励的更高而非降低的动机,并保持了灵活目标导向行为选择的能力。然而,短暂重新暴露于吗啡足以损害动机并破坏目标导向行为选择,尽管在这种情况下,大鼠仅在存在吗啡配对的上下文线索且没有反应关联反馈的情况下,才会受损,无法利用奖励价值来选择行为。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物的追求而导致成瘾。
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