Cortisol modulates the engagement of multiple memory systems: Exploration of a common NR3C2 polymorphism

Psychoneuroendocrinology. 2019 Sep:107:133-140. doi: 10.1016/j.psyneuen.2019.05.006. Epub 2019 May 15.

Abstract

Exposure to acute stress has been shown to result in a shift from declarative toward non-declarative learning, presumably mediated by brain mineralocorticoid receptors (MRs). In this study, we aimed to replicate and extend these findings by investigating the role of stress-associated cortisol secretion on learning behavior. Furthermore, we explored the influence of a well-characterized common single nucleotide polymorphism of the MR gene (rs2070951; minor allele frequency: 49.3%) previously shown to influence MR expression and HPA axis activity. Healthy males (n = 74) were exposed to the Trier Social Stress Test or a control condition prior to performing a probabilistic classification task (Weather Prediction Task). The use of a non-declarative learning strategy continuously increased over the course of the learning task after stress exposure, but leveled in the control condition. The shift toward a non-declarative strategy in the stress group was associated with better learning performance. Higher pre-stress cortisol levels favored the adoption of a non-declarative learning strategy. rs2070951 C/C-carriers in contrast to G-allele carriers exhibited a larger secretion of cortisol under stress. Furthermore, control participants homozygous for the C-allele adopted a non-declarative learning strategy less often than stressed participants, whereas the choice of strategy was independent of stress in G-allele carriers. The failure to switch strategies resulted in poorer performance, suggesting a beneficial effect of stress in dependence of MR variation. Consistent with previous findings, the results provide further support for cortisol as a driving force in coordinating the competition between multiple memory systems under stress.

Keywords: Cortisol; HPA axis; Mineralocorticoid receptor; Multiple memory systems; NR3C2; Stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Brain / metabolism
  • Cognition
  • Gene Frequency / genetics
  • Healthy Volunteers
  • Humans
  • Hydrocortisone / analysis
  • Hydrocortisone / metabolism
  • Hypothalamo-Hypophyseal System / metabolism
  • Learning
  • Male
  • Memory / physiology*
  • Pituitary-Adrenal System / metabolism
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, Mineralocorticoid / genetics*
  • Receptors, Mineralocorticoid / metabolism
  • Saliva / chemistry
  • Stress, Psychological / genetics*
  • Stress, Psychological / metabolism

Substances

  • NR3C2 protein, human
  • Receptors, Mineralocorticoid
  • Hydrocortisone