The parent-infant relationship is crucial to human personality development and sets the pattern for relationships throughout life. Inadequate or disturbed parenting is thought to contribute to the high incidence of personality, mood, anxiety, somatization and substance use disorders in our society. Investigation of the physiological basis of parenting behavior may eventually provide new medical approaches to disorders of parent-infant attachment and relationship formation. The current proposal is built upon three recent observations concerning the role of the nonapeptides oxytocin (OT) and arginine vasopressin (AVP) in the activation of maternal behavior (MB). First, site injections of nonapeptide antagonists have shown that the postpartum onset of rat MB depends upon OT and VTA receptor activation in the medial preoptic area (MPOA) and OT receptor activation in the ventral tegmental area (VTA). Second, radioligand binding assays of dissected brain tissue have demonstrated In both the MPOA and the ventral midbrain (containing the VTA) that OT binding capacity (B max) is significantly upregulated during late pregnancy in parallel with the rise in estrogen levels that occurs during that period. Third, the combined use of retrograde tracer injection into the VTA and OT immunohistochemistry has located OT perikarya that project to the VTA in the region of the dorsolateral preoptic area and the ventral bed nucleus of the stria terminalis as well as the paraventricular nucleus, two brain sites that have been implicated by lesion studies in the regulation of MB. This preliminary observation suggests that these brain sites may be the origins of an OT projection to the VTA that regulates the onset of MB.
The specific aims of the proposed project are to investigate: i) whether nonapeptide receptors in brain sites other than the MPOA and VTA are necessary for the postpartum activation of MB; 2) the location and possible estrogen receptor content of OT and AVP perikarya that project to the MPOA and OT perikarya that project to the VTA; 3) the relationships between ovarian steroid conditions that stimulate the onset of MB and nonapeptide binding, nonapeptide receptor mRNA, and nonapeptide content in brain sites where nonapeptides activate MB as well as nonapeptide content and mRNA levels in brain sites containing nonapeptide perikarya that project to the MPOA or VTA, and 4) whether nonapeptide infusion into the MPOA or VTA will stimulate the onset of MB in estrogen-primed virgin rats.
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