Date of Award

1-1-2019

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Psychology

Program

Behavioral Neuroscience

Content Description

1 online resource (viii, 164 pages) : illustrations (some color)

Dissertation/Thesis Chair

Damian G. Zuloaga

Committee Members

Christine K. Wagner, Andrew M. Poulos

Keywords

AVPV, AVPV/PeN, corticotropin releasing factor receptor 1, CRFR1, sex differences, stress, Corticotropin releasing hormone, Hypothalamic-pituitary-adrenal axis, Affective disorders, Stress (Physiology), Neuroendocrinology, Mice as laboratory animals

Subject Categories

Neuroscience and Neurobiology | Psychology

Abstract

Within the United States, women are at double the risk of men to develop a stress-related mood disorder (e.g., anxiety or depression) during their reproductive years (Kornstein et al., 2000; Kessler et al., 2005). Many factors contribute to the potential sex difference in such disorders, including gonadal hormones (hypothalamic-pituitary-gonadal axis; HPG) and how they interact with the stress response system, or hypothalamic-pituitary-adrenal (HPA) axis. Corticotropin-releasing factor (CRF) signals through binding the GS-coupled receptor, CRF receptor 1 (CRFR1), and activity between CRF/CRFR1 regulates the hormonal and behavioral stress response (Chen et al., 1993; Bale and Vale, 2004; Heinrichs et al., 1995; Smith et al., 1998; Subbannayya et al., 2013). Moreover, dysregulation of CRFR1 has been linked to the onset of stress-related mood disorders (Chrousos 2009; Garcia-Carmona et al., 2015; da Silva et al., 2016; Holly et al., 2016; Schussler et al., 2016). Antagonism or knockout of CRFR1 has been shown to reduce anxiety-like behavior (Webster et al., 1996; Smith et al., 1998; Timpl et al., 1998; Contarino et al., 1999; Tran et al., 2014; Zhao et al., 2007). While knockout or antagonism of CRF receptor 2, increases these same measurements (Bale and Vale, 2003; Bale et al., 2003; Zhao et al., 2007). Importantly, CRF has over a 10-fold higher binding affinity for CRFR1 over R2 (Perrin et al., 1995), and central CRF release is generally considered anxiogenic.

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