DRUG RESPONSES AND AROUSAL

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There is evidence that progesterone and its metabolite, allopregnanolone, may have rapid CNS actions that could play a role in the modulation of stress responses. Plasma levels of progesterone and allopregnanolone are increased in response to stressful stimuli in both animals and humans and may negatively modulate hypothalamic-pituitary-adrenal axis function. Additionally, allopregnanolone may act as an endogenous ligand of the GABAA receptor producing anxiolytic-sedative effects under physiological conditions such as stress. In the present study, we will investigate the stress dampening effects of progesterone. We will administer progesterone (25, 50 mg) or placebo to healthy male volunteers before they undergo a social stress procedure. We will assess the effects of treatments upon the consequences of acute stress, including changes in subjective state (e.g., increased anxiety or stimulation), physiological signs (heart rate and blood pressure), and plasma hormone levels (cortisol, ACTH). If confirmed in humans, the stress-dampening effect of progesterone administration and the anxiolytic efficacy of its neuroactive metabolite allopregnanolone may lead to new treatment strategies for neuropsychiatric disorders such as generalized anxiety disorder, panic disorder, depression, and drug abuse.