People who binge drink show neuroendocrine tolerance to alcohol cues that is associated with immediate and future drinking- results from a randomized clinical experiment.

Neuroendocrine tolerance to alcohol, i.e., a blunted cortisol response to alcohol, has been linked to Ventromedial Prefrontal Cortex (VmPFC) alcohol cue reactivity and relapse risk in severe Alcohol Use Disorders (AUDs), but its role in the development of AUDs is not clear. Recent work suggests that blunted cortisol responses to alcohol cues in individuals who engage in binge drinking (BD) may play a role in motivation to consume larger amounts of alcohol, but the link between this dysregulated endocrine response and BD's neural responses to alcohol cues remains unclear. To examine this, two groups of participants were recruited based on their recent drinking history. Thirty-three BD and 31 non-binging, social drinkers (SD) were exposed to alcohol cues and water cues in two separate 7 T functional magnetic resonance imaging (fMRI) scans. Each scan was followed by the Alcohol Taste Test (ATT) of implicit motivation for alcohol and a post-experiment, one-month prospective measurement of their "real world" drinking behavior. During each scan session, blood plasma was collected repeatedly to examine the separate effects of alcohol cues and alcohol consumption on cortisol levels. Relative to water cues and SD, BD demonstrated blunted cortisol cue reactivity that was negatively associated with VmPFC cue reactivity. In BD, both blunted cortisol and greater VmPFC cue reactivity were related to immediate and future alcohol consumption in the month following the scans. Thus, neuroendocrine tolerance in BD may be associated with increased incentive salience of cues and contribute mechanistically to increased alcohol consumption seen in the development of AUDs.