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.
Showing the most recent 10 out of 212 publications
