Interactive influence of sex, stressor timing, and the BclI glucocorticoid receptor polymorphism on stress-induced alterations of long-term memory

•Examined effects of stress immediately or 30 min before learning on 24-h memory.•Effects were influenced by sex and BclI variant of the glucocorticoid receptor gene.•Immediate stress enhanced memory and delayed stress impaired memory, mainly in males.•Stress enhanced memory in non-carriers of the BclI polymorphism, particularly males.•Stress impaired memory in carriers of the BclI polymorphism, particularly males. Certain susceptibility factors, such as genetic variants or specific physiological responses to stress, can dictate the effects of stress on learning and memory. Here, we examined the influence of the BclI polymorphism of the glucocorticoid receptor gene on the time-dependent effects of pre-learning stress on long-term memory. Healthy individuals were exposed to the socially evaluated cold pressor test or a control condition immediately or 30 min before word list learning. Participants’ memory for the words was tested immediately and 24 h after learning, and saliva samples were collected to genotype participants for the BclI polymorphism and to assess cortisol responses to the stressor. Results revealed that stress immediately before learning enhanced memory, while stress 30 min before learning impaired memory; these effects were largely selective to males and non-arousing words. Additionally, stress, independent of when it was administered, enhanced memory in non-carriers of the BclI polymorphism, while impairing memory in carriers; these effects were largely selective to males and participants exhibiting a robust cortisol response to stress. These results provide further evidence for time-dependent effects of stress on long-term memory and suggest that carriers of the BclI polymorphism might be more sensitive to the negative effects of corticosteroids on learning.