DHEA-S SELECTIVELY IMPAIRS CONTEXTUAL-FEAR CONDITIONING - SUPPORT FORTHE ANTIGLUCOCORTICOID HYPOTHESIS

The authors had reported that glucocorticoids play a selective role in fear conditioning. The adrenal steroid dehydroepiandrosterone (DHEA) has been reported to act as a functional antiglucocorticoid. If DHEA h as antiglucocorticoid properties, then its effects on fern conditionin g might resemble those produced by adrenalectomy. The authors now repo rt that chronic exposure to high levels of dehydroepiandrosterone sulf ate (DHEA-S; converted in vivo to DHEA) produced the same pattern of r esults as adrenalectomy. Specifically, treatment with DHEA-S impaired contextual fear conditioning 24 hr after conditioning but not immediat ely after conditioning, and like adrenalectomy, DHEA-S had no effect o n auditory-cue fear conditioning. Preexposure to the context before dr ug treatment eliminated the amnestic effects of DHEA-S, suggesting tha t, like adrenalectomy, DHEA-S exerted its effect by interfering with t he construction of a contextual memory representation. Thus, DHEA appe ars to act as a functional antiglucocorticoid in the processes that me diate learning and memory.