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A Single Administration of Dehydroepiandrosterone Does Not Enhance Memory Performance in Young Healthy Adults, but Immediately Reduces Cortisol Levels

      Dehydroepiandrosterone (DHEA), with its sulfate conjugate (DHEAS), is the most abundant steroid hormone in man (
      • Orentreich N
      • Brind JL
      • Rizer RL
      • Vogelman JH
      Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood.
      ). It is released from the adrenals, but also seems to be directly synthesized in the central nervous system (
      • Robel P
      • Baulieu E-E
      Neurosteroids biosynthesis and function.
      ), where it acts as a gamma-aminobutyric acid (GABA)A receptor antagonist (
      • Majewska MD
      Neurosteroids Endogenous bimodal modulators of the GABAA receptor. Mechanism of action and physiological significance.
      ) in animals. DHEA and DHEAS have been shown to increase neuronal excitability by reducing GABA-induced neuronal inhibition. These steroids therefore have been termed “excitatory neurosteroids” (
      • Robel P
      • Baulieu E-E
      Neurosteroids biosynthesis and function.
      ;
      • Majewska MD
      Neurosteroids Endogenous bimodal modulators of the GABAA receptor. Mechanism of action and physiological significance.
      ). Results from animal studies further indicate that GABAA-antagonistic drugs can improve memory (e.g.,
      • Castellano C
      • McGaugh JL
      Effects of post-training bicuculline and muscimol on retention Lack of state dependency.
      ). Indeed antiamnestic as well as memory-improving effects of DHEA and DHEAS could be demonstrated in mice (
      • Flood JE
      • Smith GE
      • Roberts E
      Dehydroepiandrosterone and its sulfate enhance memory retention in mice.
      ;
      • Melchior CL
      • Ritzmann RF
      Neurosteroids block the memory-impairing effects of ethanol in mice.
      ). In the latter study, DHEA blocked the memory-impairing effects of ethanol. In addition, DHEAS enhanced hippocampal primed burst potentiation, which is an electrophysiological model of neuronal plasticity (
      • Diamond DM
      • Branch BJ
      • Fleschner M
      The neurosteroid dehydroepiandrosterone sulfate (DHEAS) enhances hippocampal primed burst, but not long-term, potentiation.
      ). In humans, a single administration of DHEA to young adults was found to increase REM sleep (
      • Friess E
      • Trachsel L
      • Guldner J
      • Schier T
      • Steiger A
      • Holsboer F
      DHEA administration increases rapid eye movement sleep and EEG power in the sigma frequency range.
      ). A first open-labeled clinical trial in 6 depressed elderly patients with low DHEA levels reported an improved memory and mood after subchronic DHEA treatment (
      • Wolkowitz OM
      • Reus VI
      • Roberts E
      • Manfredi F
      • Chan T
      • Ormiston S
      • et al.
      Antidepressant and cognition-enhancing effects of DHEA in major depression.
      ); however, placebo-controlled studies in healthy subjects on the influence of DHEA on memory performance are still missing. Here we examined the effects of a single DHEA administration on memory performance in healthy men.

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