Lernmechanismen und Entwicklung der Alkoholabhängigkeit: Effekte von Alkohol auf den Erwerb und die Löschung konditionierter Reaktionen

在DFG支持的最初项目中，研究了酒精对环境中线索与奖励之间联系的获得的影响(实验1)，以及对环境中线索与奖励之间习得联系的消失的影响(实验2)。巴甫洛夫机制和工具性条件作用机制在酒依赖的形成和维持中起着重要作用。但是，尽管大量文献表明，谷氨酸能神经递质系统在线索和奖励之间的联系的获得和消失中起着关键作用，而且急性酒精对谷氨酸能系统的抑制作用是众所周知的，但还没有研究表明酒精如何影响人类的条件反射。因此，预计这些实验将有助于明确负责人类成瘾行为获得和维持的学习机制的性质。目前，实验1已经完成，对数据的分析得出了有趣的结果。我们发现，酒精对以奖励结果预期衡量的食欲条件性行为的获得没有显著影响，但当S出现时，酒精削弱了对条件性食欲反应的抑制。我们目前正在研究酒精对物种灭绝的影响；实验2正在进行中。作为我们在实验1中发现的结果，我们想提出第三个实验来调查这一结果是否仅限于条件性食欲行为，或者当出现厌恶刺激时是否也存在这一结果。在最初的研究奖学金申请中，已经引入了这一想法。随着工作的进展，显然不可能在分配给该项目的时间内进行这项实验。因此，延长研究期将是必要的，以便能够用已经为实验1和2开发的方法来研究酒精对厌恶条件反射和反应抑制的影响，并且在考虑到我们在实验1中的发现时显得尤为重要。厌恶条件反射在酒精依赖患者中扮演着重要的角色，这些患者是由于抑郁和焦虑等负面情绪而消费酒精的，因此这个项目将提供新的数据，并增强关于人类厌恶条件反射机制的现有知识。

In the original project supported by the DFG, the effects of alcohol on the acquisition of associations between cues in the environment and rewards {experiment 1), as well as on the extinction of learned associations between cues in the environment and rewards (experiment 2) are studied with moderate to heavy social drinkers. Mechanisms of Pavlovian and instrumental conditioning play an important role in the development and maintenance of alcohol dependence. But although a large body of literature suggests that the glutamatergic neurotransmitter system is critically involved in the acquisition as well as extinction of associations between cues and rewards and the inhibitory effects of acute alcohol on the glutamatergic system are well known, no studies are available to investigate how alcohol influences conditioning in humans. Thus, it is expected that these experiments will help to specify the nature of the learning mechanisms responsible for the acquisition and maintenance of addictive behaviour in humans. At present, experiment 1 is finished and the analyses of the data indicate interesting results. We found that alcohol has no significant influence on the acquisition of appetitive conditioned behaviour as measured by the expectancy of the reward outcome, but impairs the inhibition of the conditioned appetitive response when S- is presented. We currently examine the effects of alcohol on extinction; experiment 2 is in progress. As a consequence of our findings in experiment 1, we want to propose a third experiment to investigate whether this result is restricted to conditioned appetitive behaviour or if it is also present when aversive stimuli are presented. In the original application for the research fellowship this idea was already introduced. As the work progresses it has been clear that it will not be possible to carry out this experiment in the time allocated for the project. Therefore, the extension of the research fellowship would be necessary to allow the investigation of the impact of alcohol on aversive conditioning and response inhibition with the methodology already developed for experiment 1 and 2 and seems to be of special importance when taking into account our findings in experiment 1. Aversive conditioning plays an important role in alcohol dependent patients consuming alcohol due to negative emotional feelings like depression and anxiety and this project would thus provide new data and enhance current knowledge on mechanisms of aversive conditioning in humans.