Stress-induced modulation of multiple memory systems during retrieval requires noradrenergic arousal.

Abstract Stress has been shown to favor dorsal striatum-dependent ‘habit’ memory over hippocampus-dependent ‘cognitive’ memory during learning. Here, we investigated whether stress may modulate the engagement of these ‘cognitive’ and ‘habit’ systems also during memory retrieval and if so, whether such a stress-induced shift in the control of memory retrieval depends on noradrenergic activation. To this end, participants acquired a probabilistic classification learning (PCL) task that can be solved by both the ‘cognitive’ and the ‘habit’ system, reflected in the distinct behavioral strategies. Twenty-four hours later, participants received either the beta-adrenergic receptor antagonist propranolol or a placebo before they underwent a psychosocial stressor or a non-stressful control manipulation, followed by a retrieval version of the PCL task. Overall, participants showed a practice-dependent shift from ‘cognitive’ to ‘habit’ memory. Stressed participants that had received a placebo fell back to a ‘cognitive’ strategy during retrieval, which was linked to an impairment in retrieval performance. Propranolol blocked this stress-induced shift towards the less efficient strategy. Moreover, our results showed that salivary cortisol was related to the retrieval strategy only when paralleled by increased autonomic arousal. Together, these results indicate that stress effects on the modulation of multiple memory system during retrieval necessitate noradrenergic arousal, with relevant implications for retrieval performance under stress.