Remodeling of CNS Circuits--Early Oxytocin Exposure

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The purpose of this project is the analysis of neuroendocrine changes in the central nervous system as a function of neonatal manipulations of oxytocin (OT). Preliminary data from behavioral and endocrine studies suggest permanent changes in hormonal responses and in behavior, resulting from either excess OT during the neonatal period or blockade of OT receptors during this period. Such functional finding suggest the hypothesis that permanent alterations exists in the circuitry underlying these functions, this hypothesis will be examined in two animal models: domestic rats and prairie voles. Immunoreactivity for cFos, a non-specific marker for cellular activation, will be measured in the nervous system (and in some case in kidney) as a function of neonatal treatments with OT or a selective OT antagonist (OTA). Varying doses of either OT or OTA will be administered. These studies will be performed to verify the capacity of OT manipulations to influence tissue activation and to establish optimal procedures for studying the longer-term consequences of neonatal manipulations of the OT system-as part of the larger Program Project. Additional cFos studies will be conducted in adult animals using immunohistochemistry: Oxytocin (OT, OT receptors, Arginine vasopressin (AVP), AVP V1A receptors, and corticotropin releasing hormone (CrH), and receptors for estrogen (E) and progesterone (P). The latter measures will be assessed, for example, in conjunction with Project II to test the specific hypotheses that neonatal OT is capable of permanently altering sensitivity to gonadal steroids.