The Neurochemistry Core is a dual function core that will support the research efforts ofthe Projects by providing services while at the same time developing new tools and datasets that will ultimately inform each ofthe Projects. The core will provide basic histology services to document probe placements for Projects 1 and 2, and will perform quantitative oxytocin receptor (OXTR) autoradiography in rats and voles for Project 1. Th13 Core will also provide Projects 2 and 3 with novel potent and selective OXTR antagonists for their studies in nonhuman primates. In addition, the Core will play a critical role in delineating the neuroanatomical localization of OXTR in the primate brain (currently not understood). This knowledge is essential for understanding the neural mechanisms by which oxytocin (OT) modulates social cognition in Projects 2 and 3. We will use a three pronged approach for mapping the OXTR in rhesus monkey brain. First, a validated RT-PCR technique will be used to map the location of OXTR in amygdala (Amy) subnuclei as well as to determine the neuronal phenotype of OXTR neurons after single cell recording. Second, we will work to improve the selectivity of receptor autoradiography procedures in primate tissue. Finally we will continue our effort to develop and validate novel PET ligands for in vivo imaging of OXTR in living brains. If successful, the PET ligands will contribute directly to the goals of Project 2 and 3 and may ultimately be used to inform the human studies in Project 4.
These aims and the functions and services that they support are essential for the integration of research designs and interpretation of findings across projects and will provide for the first time an understanding of the neural distribution of OXTR in the primate brain. The novel OXTR antagonists and PET'ligands will have a tremendous benefit for the entire research community investigating the role of OT on social behavior.
The core will provide functions and services to each Project (including the development of novel compounds and technologies), essential for the integration of designs and findings across projects, and will provide for the first time with an understanding of the localization of OXTR in primate brain. The novel OXTR antagonists and PET ligands will have a strong impact in the field to study OT role on social primate behavior.
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|Amadei, Elizabeth A; Johnson, Zachary V; Jun Kwon, Yong et al. (2017) Dynamic corticostriatal activity biases social bonding in monogamous female prairie voles. Nature 546:297-301|
|Smith, Aaron L; Walum, Hasse; Connor-Stroud, Fawn et al. (2017) An evaluation of central penetration from a peripherally administered oxytocin receptor selective antagonist in nonhuman primates. Bioorg Med Chem 25:305-315|
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|Johnson, Zachary V; Walum, Hasse; Xiao, Yao et al. (2017) Oxytocin receptors modulate a social salience neural network in male prairie voles. Horm Behav 87:16-24|
|King, Lanikea B; Walum, Hasse; Inoue, Kiyoshi et al. (2016) Variation in the Oxytocin Receptor Gene Predicts Brain Region-Specific Expression and Social Attachment. Biol Psychiatry 80:160-169|
|Shamay-Tsoory, Simone; Young, Larry J (2016) Understanding the Oxytocin System and Its Relevance to Psychiatry. Biol Psychiatry 79:150-2|
|Johnson, Zachary V; Walum, Hasse; Jamal, Yaseen A et al. (2016) Central oxytocin receptors mediate mating-induced partner preferences and enhance correlated activation across forebrain nuclei in male prairie voles. Horm Behav 79:8-17|
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