The goal of the present proposal is to use an animal (rat) model to test the hypothesis that adverse early experience will increase physiologic stress responsivity and the expression of behaviors that are known cardiovascular risk factors in adulthood while beneficial experience will reduce both. We will also test the hypothesis that reduced central serotonergic activity will be associated with and contribute to these changes. To test this hypothesis, we will evaluate neuroendocrine, cardiovascular and behavioral responsivity to stressors during ontogeny and in adult life following daily brief or prolonged separation from the dam. We plan to expose developing rats to daily brief (15 min) or prolonged (6 hrs) separation from the dam on postnatal days 2-7, and to evaluate neuroendocrine (ACTH, corticosterone, prolactin) responses to restraint stress, heart rate and blood pressure (adult only) and peripheral norepinephrine turnover in response to restrain stress and locomotor responses in a novel environment. In addition, aggression and alcohol consumption will be evaluated in adulthood following the same experience. To evaluate the effect of early experience on serotonergic function, we will determine 5HIAA:5HT ratios and determine the prolatin and PHA response response to a fenfluramine challenge in adults following the same paradigm. The role of serotonin will be explored further by evaluating these same indices in animals in which serotonin is depleted pharamacologically with PCPA during the same critical phase in development or in adulthood. These studies should provide considerable insight into the role of early life experience in the constellation of biobehavioral factors (HPA reactivity, sympathetic reactivity, aggression/hostility, alcohol consumption) that have been associated with increased risk of cardiovascular disease in human. In addition, these experiments will provide insight into role of central serotonergic neurons as a mediator of these effects.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Singh, Abanish; Babyak, Michael A; Brummett, Beverly H et al. (2018) Developing a synthetic psychosocial stress measure and harmonizing CVD-risk data: a way forward to GxE meta- and mega-analyses. BMC Res Notes 11:504
Ward-Caviness, Cavin K; Kraus, William E; Blach, Colette et al. (2018) Associations Between Residential Proximity to Traffic and Vascular Disease in a Cardiac Catheterization Cohort. Arterioscler Thromb Vasc Biol 38:275-282
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Jiang, Rong; Babyak, Michael A; Brummett, Beverly H et al. (2017) Brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism is associated with disease severity and incidence of cardiovascular events in a patient cohort. Am Heart J 190:40-45
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Ward-Caviness, Cavin K; Neas, Lucas M; Blach, Colette et al. (2016) Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease. PLoS One 11:e0152670
McGarrah, Robert W; Craig, Damian M; Haynes, Carol et al. (2016) High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort. Atherosclerosis 246:229-35
Ogle, Christin M; Rubin, David C; Siegler, Ilene C (2016) Accounting for Posttraumatic Stress Disorder Symptom Severity With Pre- and Posttrauma Measures: A Longitudinal Study of Older Adults. Clin Psychol Sci 4:272-286

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