DESCRIPTION (provided by applicant): A classical view claims that oxytocin (OT) fosters affiliative behaviors and arginine vasopressin (VP) enhances aggression. But a lot of data conflict with this. The confusion is not due purely to neuroanatomical details, or gender or species. I will use two novel approaches to compare OT and VP responsive systems: (I.) Using molecular tools and some new behavioral thinking; and (II.) Using estrogens (E) as biologically relevant probes. In order to take maximal advantage of genetic knowledge and preliminary evidence we will use female mice. Specifically: Aim I. I will perturb OT gene expression and OT receptors using gene knockouts - with all interesting results followed up by a novel antisense DNA technique - and measure an interesting behavior maternal aggression (as part of reproduction), compared to an 'affiliative behavior', maternal care compared to testosterone-facilitated aggression. (I have already shown that seminatural environment living helps to reveal hitherto unrealized behavioral phenotypes.) Aim II. Estrogenic regulations of these systems offer the opportunity to probe with novel E-related molecular tools. Will ER gene knockout mice, antisense oligos, and selective agonists and antagonists change the three behaviors above in the predicted directions? Aim III. Will verify major discoveries of this project in normal pregnant and lactating mice. In all Aims, important targets for molecular manipulations will be in the amygdala: The basolateral nuclei are involved in fear; the central nucleus in anxiety; and the mediocortical region in signaling by pheromones. All of these functions could influence the three behaviors measured in this project. Also important: The dorsolateral preoptic area for maternal behavior, and the dorsal raphe for serotonin and aggression. This project uses the multidisciplinary capacity of my laboratory and the Rockefeller University campus, and is written in an "if/then" style to show how we will maximize the impact of 5 years of work. These experiments will increase our understanding of two extremely important transcriptional systems, OT and VP, with widespread projections and significant autonomic and behavioral effects. Impact: OT may be involved in postpartum depression. OT systems certainly facilitate social recognition, disorders of which are prominent in autism and in schizophrenia.