Acute Social Stress Potentiates Cue-Driven Behavior in Alcohol Use Disorder: Behavioral and Neural Evidence
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Background
Pavlovian-to-instrumental transfer (PIT) describes how conditioned cues shape instrumentally learned behavior and has been linked to cue-driven alcohol seeking and relapse in alcohol use disorder (AUD). Acute psychosocial stress is an established relapse risk factor that may amplify cue-driven motivational control. Whether acute stress modulates PIT behaviorally and neurally, and whether this differs in AUD, remains unclear.
Methods
Within the TRR265 study, 109 participants (62 AUD, 46 controls (CON)) completed a within-subject, randomized, two-day PIT paradigm under Trier Social Stress Test and placebo conditions, with repeated salivary cortisol sampling across sessions. A subsample (n = 62; 34 AUD, 28 CON) underwent fMRI during the transfer phase.
Results
A robust PIT effect emerged across groups, and acute stress significantly enhanced cue- driven response vigor (p = .034), with no AUD-specific behavioral effect. Exploratorily, cortisol responders showed stronger stress-related PIT enhancement than non-responders (p = .022). Neurally, PIT engaged the right amygdala during placebo. Acute stress induced less downregulation of PIT- related left amygdala activity in AUD than in CON (p FWE = .019), with no group difference during placebo.
Conclusions
Acute psychosocial stress potentiated the motivational influence of non-drug-related conditioned cues on behavior irrespective of AUD status, identifying PIT as a candidate mechanism through which stress may promote alcohol-seeking behavior. Despite comparable behavioral effects, AUD was associated with blunted stress-induced downregulation of PIT-related amygdala activity, suggesting altered neural regulation of cue-driven processing whose relevance for future alcohol consumption and clinical outcome remains to be established.
