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"LEARNING BIASES AND ELEVATED REACTIVITY IN WISTAR KYOTO RATS: FURTHERING AN ANIMAL MODEL OF ANXIETY VULNERABILITY"

by
Thomas M. Ricart
MD/PhD Program
B.S. 2005, The College of New Jersey, Ewing, NJ



Thesis Advisor: Richard J. Servatius, Ph.D.
Professor
Department of Neurology and Neurosciences
VA Medical Center

Friday, July 16, 2010
11:00 A.M., East Orange VA Hospital, 11th Fl., Conference Room (11-137)


Abstract

The focus basic science understanding of anxiety disorders has recently shifted from the role of stressors (adverse life experiences) to the interaction of vulnerabilities and predispositions with stressors. With this shift, a great deal is unknown concerning how vulnerabilities serve to interact with stressors enhancing risk. The control over stressor presentation and challenges in animal models allows one to isolate pre-existing tendencies from the changes arising in the aftermath of stress. One source of vulnerability or anxiety disorders is inhibited temperament. Inbred Wistar Kyoto (WKY) rats model inhibited temperament, displaying withdrawal in the face of social and novel non-social challenges. These rats also acquire avoidance faster than outbred Sprague Dawley (SD) rats, a standard behavioral control for the WKY rat. It is the acquisition of avoidance (emotional, behavioral or cognitive) that describes the development of anxiety in humans. Accordingly, learning biases exhibited by WKY rats reflect learning biases exhibited by humans. Thus, this dissertation has two major goals. The first goal was to evaluate learning biases toward understanding faster avoidance learning in WKY rats. The second goal was to examine how the acquisition of avoidance may interact with other symptoms of anxiety disorders. Investigation into the first aim revealed a number of learning biases in WKY rats. WKY rats demonstrate reduced proactive interference, that is, they exhibit uninhibited learning under conditions which should reduce learning. Reduced proactive interference is also seen in humans with anxiety. They also demonstrate facilitated classical conditioning compared to SD rats, suggesting that enhanced associative learning may underlie greater avoidance learning. Moreover, WKY rats are more sensitive to negative reinforcement. Investigation into the second aim revealed that greater arousal, a key symptom of anxiety disorders, is evident in both male and female WKY rats before avoidance learning, suggesting arousal as a potential anxiety vulnerability factor. In addition, in response to stress associated with avoidance learning, arousal is further increased in male WKY rats but is decreased in female WKY rats, suggesting distinct symptomology in males and females with anxiety disorders. These findings provide valuable insights into anxiety vulnerability that deserve further testing in human research.


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