Actions of 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 receptors. DHEA(S) increases neuronal excitability, enhances neuronal plasticity and also has neuroprotective properties. In line with these observations DHEA(S) treatment in rodents enhances memory in several paradigms. Even more studies show antiamnestic effects of the steroids. However, DHEA(S) has also anxiolytic and anti-aggressive properties. In humans cross-sectional and longitudinal studies suggest that DHEAS might be associated with global measures of well-being and functioning; however, a relationship with cognition could not be detected to date. Moreover, studies investigating DHEAS levels in neurodegenerative diseases have produced conflicting results. Experimental studies in elderly humans have revealed preliminary evidence for mood enhancing and antidepressant effects of DHEA treatment, while positive effects on measures of memory and attention could not be found. However, electrophysiological studies demonstrated that DHEA treatment has effects on the human CNS. Several reasons for the discrepancy between data obtained in rodents and humans are discussed and research perspectives are outlined which might help to improve interpretation of results obtained in the two species.