Opioid and dopaminergic mechanisms in the learning of safety

Fear is the emotional reaction that accompanies an expectation of danger. But what if the expectation is wrong and the danger doesn’t follow? Numerous experiments have shown that rodents lose their fears when a previous signal of danger is no longer followed by this danger. The reduction of fear results from new learning of safety, in which the signal becomes associated with the absence of danger. This new learning is governed by the degree of expectancy-violation during the absence of danger. A stronger expectation of danger will evoke a stronger violation during its absence, and more safety learning will occur. But what exactly happens during violations of danger expectations has only recently become clear. Rodent optogenic and microdialysis studies have pinpointed a key role for the mesolimbic dopamine-reward system in driving safety learning during omissions of expected danger. In this project, we will test in rodents the hypothesis that the opioidreward system is involved as well, and we will investigate its interaction with the dopamine system during expectancy-violation processing. For that purpose, we will use a combination of pharmacological, microdialysis and electrophysiological recording techniques. Our hope is that more insight into the role of the opioid system in the learning of safety will help optimizing treatments for anxious individuals with compromised safety learning.