Deans

Lisa Deziel, Ph.D., Pharm.D. – College of Pharmacy

Award Date

1-1-2015

Abstract

Post-traumatic stress disorder (PTSD), defined as recurring distress that disrupts one's work or home-life after a traumatic event, is a significant societal problem. The National Institutes of Mental Health reports that 7.7 million adults over 18 suffer from PTSD. It afflicts a disproportionate number of military veterans (19% of Vietnam War Veterans; Dohrenwend,2006) from combat stress and injuries, or other traumatic events such as sexual assaults. Treatments for this disorder are limited to counseling and symptomatic medication. It is not known why some people develop PTSD, while others do not. A complication of PTSD is high blood pressure (hypertension). A common denominator between hypertension and psychological stress disorders is angiotensin II (AngII). Systemically, AngII constricts blood vessels and promotes salt retention. Centrally, AngII promotes thirst, salt appetite, sympathetic nervous system activation (fight or flight response) and anxiety. Previous studies of Marvar and colleagues (Khoury,2012 and Marvar,2013) indicate that inhibitors of AngII receptors, or blockers of AngII formation decrease PTSD symptoms in humans and fear-related responses in mice. To localize the brain regions involved in the therapeutic actions of these anti-AngII agents, transgenic mice in which the gene for the major AngII receptor can be turned off by microinjection of a modified virus, will be used. These mice will undergo fear conditioning with subsequent testing for expression of a fear response (freezing of movement) and extinction of this response, in comparison to normal mice. To verify brain region-specific loss of AngII receptors, brains of the mice from these studies will be evaluated for Ang II receptor expression using receptor autoradiography as described previously (Speth,1999). It is hypothesized that brain region-specific deletion of this AngII receptor will reduce the fear response. These studies will help to determine the brain region(s) in which AngII may act to promote development of PTSD.

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