Modulation of spatial and stimulus-response learning strategies by exogenous cortisol in healthy young women

Glucocorticoids (GCs) are known to influence learning and memory processes. While most studies focus on the effects of GCs on the performance within a single memory system, we asked whether GCs modulate also the transition between hippocampus-dependent spatial and caudate nucleus-dependent stimulus-response memory systems. Eighty-four young healthy women received a placebo, 5 or 30 mg hydrocortisone orally. One hour later, participants were asked to locate a win-card in a 3D model of a room. The card could be located via two strategies: spatial (multiple distal cues) and stimulus-response (a single proximal cue). Relocation of the proximal cue after 12 trials revealed the strategy, number of trials to learning criterion the performance. As expected, more trials were needed to acquire the task with hydrocortisone. Remarkably, hydrocortisone switched the use of learning strategies towards more spatial learning (dose-dependently: placebo 4% < 5 mg 21%< 30 mg 32%), independent of autonomic and subjective arousal. The learning curves of spatial and stimulus-response learners were comparable. Our results demonstrate that exogenous GCs prior to learning affect the performance within a memory system and also coordinate the use of multiple memory systems. Taking into account this dual action of GCs will contribute to a better understanding of stress (hormone) effects on learning and memory.