Browsing by Author "Arendt, David H."

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    High Throughput Modeling of Post-Traumatic Stress Disorder
    (Office of the Vice Chancellor for Research, 2015-04-17) Villegas, Jhilari I.; Arendt, David H.; Johnson, Philip J.
    Combat veterans, have higher instances of PTSD only about 7% of the US population will develop this pathology. The low ratio of individuals exposed to a traumatic event to individuals who develop PTSD (75%: 7%) highlights that most individuals can successfully cope with the emotional aftermath of stressful situations. Individuals suffering from PTSD seem to have a fundamental impairment in this stress coping ability, or the ability to progress past the event. It is common for people to report PTSD like symptoms in the following days or weeks after a traumatic event and is considered to be perfectly natural. It is not until these symptoms persist for more than a month before a diagnosis of PTSD can be made. Given the incidence of natural disasters, violent/sexual assaults, and other traumatic incidents in the United States, there is a great need to develop tools directed at studying PTSD. Preclinical modeling of PTSD can be achieved by using Pavlovian fear conditioning where a rat associates a mild foot shock with neutral tone. Details associated with a past traumatic can elicit a fearful reaction in PTSD, the tone previously paired with foot shock can elicit a fearful response in a rat, when not presented with a shock. The ability of an animal to disassociate the tone from the foot shock can be achieved by repeated exposure to the tone in the absence of the shock. After this repeated exposure to the tone the animal learns to “extinguish” the previous fearful memory of the footshock is very relevant to PTSD which is characterized by fearful memories that persist for an extended period of time. In the current work, we characterize a new apparatus for fear conditioning / extinction in rats that allows for the running of multiple animals paired with automated behavioral scoring.
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    Nuance and behavioral cogency: How the Visible Burrow System inspired the Stress-Alternatives Model and conceptualization of the continuum of anxiety
    (Elsevier, 2015-07-01) Robertson, James M.; Prince, Melissa A.; Achua, Justin K.; Carpenter, Russ E.; Arendt, David H.; Smith, Justin P.; Summers, Torrie L.; Summers, Tangi R.; Summers, Cliff H.; Department of Psychiatry, IU School of Medicine
    By creating the Visible Burrow System (VBS) Bob Blanchard found a way to study the interaction of genetics, physiology, environment, and adaptive significance in a model with broad validity. The VBS changed the way we think about anxiety and affective disorders by allowing the mechanisms which control them to be observed in a dynamic setting. Critically, Blanchard used the VBS and other models to show how behavioral systems like defense are dependent upon context and behavioral elements unique to the individual. Inspired by the VBS, we developed a Stress Alternatives Model (SAM) to further explore the multifaceted dynamics of the stress response with a dichotomous choice condition. Like the VBS, the SAM is a naturalistic model built upon risk assessment and defensive behavior, but with a choice of response: escape or submission to a large conspecific aggressor. The anxiety of novelty during the first escape must be weighed against fear of the aggressor, and a decision must be made. Both outcomes are adaptively significant, evidenced by a 50/50 split in outcome across several study systems. By manipulating the variables of the SAM, we show that a gradient of anxiety exists that spans the contextual settings of escaping an open field, escaping from aggression, and submitting to aggression. These findings correspond with increasing levels of corticosterone and increasing levels of NPS and BDNF in the central amygdala as the context changes.Whereas some anxiolytics were able to reduce the latency to escape for some animals, only with the potent anxiolytic drug antalarmin (CRF1R-blocker) and the anxiogenic drug yohimbine (α2 antagonist) were we able to reverse the outcome for a substantial proportion of individuals. Our findings promote a novel method for modeling anxiety, offering a distinction between low-and-high levels, and accounting for individual variability. The translational value of the VBS is immeasurable, and it guided us and many other researchers to seek potential clinical solutions through a deeper understanding of regional neurochemistry and gene expression in concert with an ecological behavioral model.