Role of Allopregnanolone in Mediating the Adverse Effects of Psychosocial Stress

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DESCRIPTION (provided by applicant): The incidence of mood disorders, such as anxiety and depression, in women is twice that in men. Moreover, women are susceptible to a distinct group of mood disorders that are associated with fluctuations in ovarian hormone levels, including premenstrual dysphoric disorder, postpartum depression, and hormone replacement therapy induced negative mood. A precipitating factor in these disorders may be chronic exposure to psychosocial stressors and increased activation of the body?s primary stress axis. The occurrence of these mood disorders in women is complicated by the presence of other adverse health outcomes. Notably, eating disorders, such as emotional eating and obesity, are highly co-morbid with affective disorders, having similar disruptions in neurobiological systems present within individuals diagnosed with mood disorders. The long-term objective of the proposal is to elucidate the mechanisms by which progestagens modulate the disruption of stress axis and the serotonergic (5HT) system, both of which have been implicated in the etiology of mood and eating disorders in women. The central goal of this proposal is to implicate the disruption of allopregnanolone (ALLO), a specific progesterone, levels as a critical player in the disruption of systems associated with increased emotional and stress axis reactivity characteristic of affective disorders. The first aim is to evaluate how progestagens modulate socially induced changes in emotional reactivity and appetite. The second aim is to determine whether changes in ALLO and associated behavioral phenotypes are due to stress-induced activity. We will make use of an ethologically relevant model of psychosocial stress, employing hormonal and pharmacological means to assess emotional behavior and preference for a high calorie diet. PUBLIC HEALTH RELEVANCE: Women are twice as susceptible as men to mood and eating disorders, including anxiety, depression, obesity, and emotional eating. Studying the mechanisms by which psychosocial stress disrupts the actions of ovarian hormones will speak to the development of anxiety-based psychopathology in women.