Hindawi Publishing Corporation Neural Plasticity Volume 2009, Article ID 904568, 15 pages doi:10.1155/2009/904568 Research Article Viral Vector Induction of CREB Expression in the Periaqueductal Gray Induces a Predator Stress-Like Pattern of Changes in pCREB Expression, Neuroplasticity, and Anxiety in Rodents Robert Adamec, 1 Olivier Berton, 2 and Waleed Abdul Razek 1 1 Department of Psychology, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada A1B 3X9 2 Faculty of Behavioral Pharmacology, University of Pennsylvania, Room 2218 125, S 31ST (TRL) Philadelphia, PA 19104-3403, USA Correspondence should be addressed to Robert Adamec, radamec@mun.ca Received 25 June 2008; Accepted 5 January 2009 Recommended by Thelma A. Lovick Predator stress is lastingly anxiogenic. Phosphorylation of CREB to pCREB (phosphorylated cyclic AMP response element binding protein) is increased after predator stress in fear circuitry, including in the right lateral column of the PAG (periaqueductal gray). Predator stress also potentiates right but not left CeA-PAG (central amygdala-PAG) transmission up to 12 days after stress. The present study explored the functional significance of pCREB changes by increasing CREB expression in non-predator stressed rats through viral vectoring, and assessing the behavioral, electrophysiological and pCREB expression changes in comparison with handled and predator stressed controls. Increasing CREB expression in right PAG was anxiogenic in the elevated plus maze, had no effect on risk assessment, and increased acoustic startle response while delaying startle habituation. Potentiation of the right but not left CeA-PAG pathway was also observed. pCREB expression was slightly elevated in the right lateral column of the PAG, while the dorsal and ventral columns were not affected. The findings of this study suggest that by increasing CREB and pCREB in the right lateral PAG, it is possible to produce rats that exhibit behavioral, brain, and molecular changes that closely resemble those seen in predator stressed rats. Copyright © 2009 Robert Adamec et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1. Introduction Study of the neurobiology of long-lasting changes in affect occurring after stressful events is of interest, an interest heightened by the fact that fearful events may precipitate affective psychopathologies [1, 2]. In extreme cases, a single aversive experience may induce posttraumatic stress disorder (PTSD) [3, 4]. Animal models are useful to enhance understanding of the impact of stress on brain and behavior, permitting simulation of a human condition in a controlled setting allowing study of disorder development. Conditioned fear paradigms, behavior in unfamiliar situations that are fear or anxiety provoking, and more recently, predator stress, are all models used to understand the neurobiology of the impact of fearful events on affect. Predator stress in our hands involves the unprotected exposure of a rat to a cat [5]. Predator stress may model aspects of PTSD for several reasons. First, predator stress has ecological validity due to the natural threat posed by the predatory nature of the stressor. Second, duration of anxiety-like effects in rats after predator stress, as a ratio of life span, is comparable to the DSM IV duration of psychopathology required for a diagnosis of chronic PTSD in humans. Third, predator stress has neurobiological face validity in that right amygdala and hippocampal circuitry are implicated in behavioral changes produced by predator stress, and these areas are consistent with brain areas thought to be involved in PTSD [6–9]. For example, brain imaging implicates hyperexcitability of the right amygdala in response to script-driven trauma reminders in the etiology of PTSD [10–14]. Fourth, parallel path analytic studies using data from Vietnam veterans suffering from PTSD and predator stressed rodents find that in both humans and rodents, features of the stressor predict the level of anxiety [6]. For example, in predator stressed animals, the more cat bites received, the higher the level of anxiety measured a