A proposed role for glucocorticoids in mediating dopamine-dependent cue-reward learning

Learning to respond appropriately to one's surrounding environment is fundamental to survival. Importantly, however, individuals vary in how they respond to cues in the environment and this variation may be a key determinant of psychopathology. The ability of seemingly neutral cues to promote maladaptive behavior is a hallmark of several psychiatric disorders including, substance use disorder, post-traumatic stress disorder, eating disorders and obsessive-compulsive disorder. Thus, it is important to uncover the neural mechanisms by which such cues are able to attain inordinate control and promote psychopathological behavior. Here, we suggest that glucocorticoids play a critical role in this process. Glucocorticoids are primarily recognized as the main hormone secreted in response to stress but are known to exert their effects across the body and the brain, and to affect learning and memory, cognition and reward-related behaviors, among other things. Here we speculate that glucocorticoids act to facilitate a dopamine-dependent form of cue-reward learning that appears to be relevant to a number of psychiatric conditions. Specifically, we propose to utilize the sign-tracker/goal-tracker animal model as a means to capture individual variation in stimulus-reward learning and to isolate the role of glucocorticoid-dopamine interactions in mediating these individual differences. It is hoped that this framework will lead to the discovery of novel mechanisms that contribute to complex neuropsychiatric disorders and their comorbidity.