Drawbacks to strengthening neural salience encoding: a link between cortisol and risky drinking

Emotionally salient experiences are encoded and remembered more strongly, an effect that can be amplified by hormones like cortisol. Such memories can in turn profoundly influence later behavior. However, little is known about the link between amplified salience encoding and subsequent behavior. This pathway may be particularly important for risky alcohol drinking, which has been linked to sensitized salience responses, memory, and cortisol. To test this possibility, we integrated pharmacology using a double-blind cross-over design with fMRI, cognitive, and motivation assays across a range of healthy male and female social drinkers. As anticipated, cortisol enhanced memory for salient alcohol-related events; critically, this bias was in turn associated with later alcohol motivation. Increased alcohol motivation was particularly pronounced in more susceptible risky drinkers, for whom cortisol enhanced brain salience responses to alcohol. These sensitized salience responses predicted both memory biases and alcohol motivation. Together, these findings reveal maladaptive consequences of enhanced salience encoding. Significance Statement Our memories for salient experiences can strongly influence what we choose to do. Despite the importance of such memories for motivated behaviors like alcohol drinking, the mechanisms by which salient memories are strengthened and influence later behavior are unclear. In the current study, we integrated findings from human research (glucocorticoids enhance salient memory encoding) with findings from rodent models (glucocorticoids enhance alcohol motivation, especially with a history of ethanol exposure) to examine whether these processes are linked in humans. We found evidence for this pathway: hydrocortisone amplified brain signatures of salience (particularly for participants who drank more), which predicted enhanced memory. Both brain salience and enhanced memory predicted increased alcohol motivation. This translational pathway reveals downsides to amplifying salient memories.