Leung Hiu T, Corbit Laura H
School of Psychology, University of Sydney, Australia.
Addict Biol. 2017 Jan;22(1):47-57. doi: 10.1111/adb.12267. Epub 2015 May 14.
Alcohol-related stimuli can trigger relapse of alcohol-seeking behaviors even after extended periods of abstinence. Extinction of such stimuli provides a means for reducing their impact on relapse. However, the expression of extinction can be disrupted by exposure to the previous reinforcer as well as the simple passage of time. We investigated whether augmentation of prediction error or of noradrenaline neurotransmission by the reuptake inhibitor atomoxetine would enhance long-term extinction of alcohol-seeking behavior. Rats received Pavlovian conditioning of multiple stimuli signaling the delivery of an alcohol reward before individual extinction was given to each of these stimuli. Further extinction was then given to a target stimulus presented in compound with another alcohol-predictive stimulus intended to augment prediction error (Experiment 1) or after a systemic injection of atomoxetine (1.0 mg/kg; Experiment 2). Experiment 3 examined whether the compound stimulus effect relied on noradrenergic activity by testing the effects of the β-adrenergic antagonist propranolol, given prior to compound stimulus trials. Long-term retention of extinction learning was assessed a week later. Compound stimulus presentations enhanced long-term extinction as the stimulus extinguished in compound elicited less responding than a stimulus receiving equal extinction alone when tested a week later. This effect was mimicked by atomoxetine and blocked by propranolol given during extinction training. Thus, extinction of alcohol-seeking behavior can be improved by extinguishing multiple alcohol-predictive stimuli or enhancing noradrenaline neurotransmission during extinction training. Both behavioral and neurobiological processes could be exploited to enhance the outcome of extinction-based treatments for alcohol use disorders.
即使经过长时间戒酒，与酒精相关的刺激仍可引发觅酒行为的复发。消除此类刺激为减少其对复发的影响提供了一种方法。然而，这种消除的表现可能会因接触先前的强化物以及时间的简单流逝而受到干扰。我们研究了通过再摄取抑制剂托莫西汀增强预测误差或去甲肾上腺素神经传递是否会增强觅酒行为的长期消除。在对每种刺激进行单独消除之前，大鼠接受了多种信号提示酒精奖励发放的巴甫洛夫条件反射。然后，对与另一种酒精预测性刺激复合呈现的目标刺激进行进一步消除，以增强预测误差（实验1），或在全身注射托莫西汀（1.0毫克/千克）后进行（实验2）。实验3通过测试在复合刺激试验前给予β-肾上腺素能拮抗剂普萘洛尔的效果，研究复合刺激效应是否依赖于去甲肾上腺素能活性。一周后评估消除学习的长期保持情况。复合刺激呈现增强了长期消除，因为一周后测试时，与单独接受相同消除的刺激相比，在复合中消除的刺激引发的反应更少。这种效应在托莫西汀给药时得到模拟，并在消除训练期间被普萘洛尔阻断。因此，通过消除多种酒精预测性刺激或在消除训练期间增强去甲肾上腺素神经传递，可以改善觅酒行为的消除。行为和神经生物学过程均可被利用来提高基于消除的酒精使用障碍治疗的效果。
