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

在DFG支持的原始项目中，酒精对环境中线索和奖励之间关联的获得的影响（实验1），以及对环境中线索和奖励之间习得关联的消失（实验2）的影响研究了中度到重度社交饮酒者。巴甫洛夫条件反射和工具条件反射的机制在酒精依赖的发展和维持中起重要作用。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关联的获得和消失中起着至关重要的作用，并且急性酒精对谷氨酸能系统的抑制作用是众所周知的，但没有研究可以调查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的获得和维持的学习机制的性质。目前，实验1已经完成，数据分析显示出有趣的结果。我们发现，酒精对食欲条件行为的习得没有显著影响，这是通过对奖励结果的期望来衡量的，但当S-出现时，酒精会损害条件食欲反应的抑制。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。由于我们在实验1中的发现，我们想提出第三个实验来研究这个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。在最初的研究奖学金申请中，这个想法已经被引入。随着工作的进展，很明显，在分配给项目的时间内不可能进行这项实验。因此，研究奖学金的扩展是必要的，以便使用实验1和2中已经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，考虑到我们在实验1中的发现，这似乎特别重要。厌恶条件反射在酒精依赖患者因抑郁和焦虑等负面情绪而饮酒中起着重要作用，因此该项目将提供新的数据并增强对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.