Adrenal androgens, DHEA and DHEA-S, are neurosteroids and non-competitive negative modulators of the GABA-benzodiazepine receptor complex. It is also known that chronic smoking and smoking cessation influence plasma DHEA and DHEA-S concentrations. However, the acute effects of smoking on DHEA/DHEA-S concentrations are unknown. We have hypothesized that in habitual smokers, smoking induces a frequent release of DHEA and DHEA-S which in turn leads to altered responsiveness of the hypothalamo-pituitary-adrenal axis. To test this we intend to do a series of three studies to determine circadian rhythms, integrity of the HPA axis, acute effects of smoking and potential changes in GABAergic activity.
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