Actions of del dehydroepiandrosterone and its sulfate in the central nervous system: effects on cognition and emotion in animals and humans

Dehydroepiandrosterone (DHEA) and its sulfate ester, DHEAS, exert multiple effects in the rodent central nervous system (CNS). Most of them seem to be mediated through their non-genomic action on several neurotransmitter rece ptors. DHEA(S) increases neuronal excitability, enhances neuronal plasticit y and also has neuroprotective properties. In Line with these observations DHEA(S) treatment in rodents enhances memory in several paradigms. Even mor e studies show antiamnestic effects of the steroids. However, DHEA(S) has a lso anxiolytic and anti-aggressive properties. In humans cross-sectional an d longitudinal studies suggest that DHEAS might be associated with global m easures of well-being and functioning; however, a relationship with cogniti on could not be detected to date. Moreover; studies investigating DHEAS lev els in neurodegenerative diseases have produced conflicting results. Experi mental studies in elderly humans have revealed preliminary evidence for moo d enhancing and antidepressant effects of DHEA treatment, while positive ef fects on measures of memory and attention could not be found. However, elec trophysiological studies demonstrated that DHEA treatment has effects on th e human CNS. Several reasons for the discrepancy between data obtained in r odents and humans are discussed and research perspectives are outlined whic h might help to improve interpretation of results obtained in the two speci es. (C) 1999 Published by Elsevier Science B.V. All rights reserved.