Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Charité Mitte, Berlin, Germany.
Social and Preventive Medicine, Humanwissenschaftliche Fakultät, Area of Excellence Cognitive Sciences, University of Potsdam, Am Neuen Palais 10, 14469, Potsdam, Germany.
Eur Arch Psychiatry Clin Neurosci. 2019 Apr;269(3):295-308. doi: 10.1007/s00406-017-0860-4. Epub 2018 Jan 8.
The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = - 3.86, p < .001), but not in healthy controls (t = - 0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.Clinical trial: LeAD study, http://www.lead-studie.de , NCT01679145.
巴甫洛夫条件刺激对持续行为的影响可能有助于解释酒精线索如何刺激药物寻求和摄入。我们使用条件性-操作性条件反射转移任务，研究了与酒精相关的线索对接近行为（即操作性反应行为）及其神经相关性的影响，并与酒精依赖患者脱毒后的复发相关。31 名最近脱毒的酒精依赖患者和 24 名健康对照者接受了操作性训练，在该训练中，接近或不接近最初的中性刺激会得到金钱奖励。在功能磁共振成像（fMRI）期间，使用背景中呈现的与酒精相关或中性刺激（作为条件性刺激）进行了消退测试。随后对患者进行了 6 个月的随访。我们观察到，与酒精相关的背景刺激抑制了脱毒酒精依赖患者的接近行为（t=-3.86，p<.001），但对健康对照组没有影响（t=-0.92，p=.36）。这种行为抑制与伏隔核（NAcc）的神经激活有关（t=2.06，p<.05）。有趣的是，这两种影响仅存在于随后的戒断者中，而不存在于复发者和依赖程度较轻者中。我们的数据表明，尽管与酒精相关的线索伴随着更强的 NAcc 激活，但它们可以获得类似于厌恶刺激的抑制性行为特征，表明了显著归因。这些发现仅限于戒断和较轻疾病的事实表明，它们可能是潜在的恢复力因素。临床试验：LeAD 研究，http://www.lead-studie.de，NCT01679145。
