PHD, Kent State University, 2015, College of Arts and Sciences / Department of Biological Sciences
Psychological illnesses such as anxiety disorder, depression, and posttraumatic stress disorder share a common element: patients often engage in rumination, which is characterized by intrusive thoughts and persistent memory of negative events. Indeed, a hallmark of the stress response is the enhanced capability for learning in emotionally salient situations, especially those involving aversive stimuli. A rodent model of chronic mild stress (CMS) was used in this series of experiments to examine effects on associative learning and behavior, mediated through stimulation of central beta-adrenergic receptors (β-ARs). Animals exposed to CMS develop behaviors associated with depression (e.g. decreased exploration, social withdrawal) and fear (freezing in a pertinent context) when observed in a place with environmental cues associated with the stress paradigm; when observed in a place without such cues, no such manifestation occurs. Interestingly, we also found that prolonged exposure to stress decreases behavioral inhibition, as stressed rodents placed in a passive avoidance apparatus show decreased retention latencies 24h post training, relative to home cage controls. We also investigate the role of β-ARs, where we found that administration of the beta blocker propranolol attenuates or blocks the development of these depressive behaviors and also prevents the stress-enhanced learning shown in a contextual fear conditioning task; however, β-AR involvement is more complex in passive avoidance. A final study suggests that chronic exposure to stress may sensitize β-adrenergic receptor signaling, as we observed an increase in amygdaloid adenylate cyclase activity in stressed subjects, which was blocked with the use of propranolol; however, further results were inconclusive. Overall, we conclude that stress-induced anxiety and depressive behaviors initially develop as a consequence of the enhanced learning that is a part of the stress response, and that the effect is mediated (open full item for complete abstract)
Committee: John Johnson PhD (Advisor); Heather Caldwell PhD (Committee Member); Eric Mintz PhD (Committee Member); Aaron Jasnow PhD (Committee Member); David Riccio PhD (Other)
Subjects: Biology; Neurobiology; Neurosciences; Physiological Psychology; Physiology