The role of the hypothalamic-pituitary-adrenocortical axis in memory-related effects of anxiolytics

Two major classes of antianxiety drugs, benzodiazepines and partial agonists of 5-HT1A receptors, have dissimilar effects on learning. Benzodiazepines induce amnesic effects in humans and animals. In contrast, partial agonists of 5-HT1A receptors do not suppress memory in humans and have variable effects in animal learning models. The two groups of drugs shift activity of the hypothalamic-pituitary-adrenocortical (HPA) axis in opposite ways. Benzodiazepines, given at antianxiety doses, suppress HPA axis excitability. Partial agonists of 5-HT1A receptors facilitate HPA excitability and, at higher doses, directly stimulate ACTH secretion. Assuming that certain components of the HPA axis are involved in memory acquisition, it is hypothesized that antianxiety drugs may affect learning through the regulation of HPA axis excitability.