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Novel targets, biomarkers, and models in the neurobiology of anxiety Open Access


Other title
animal behavior models
Type of item
Degree grantor
University of Alberta
Author or creator
Yeung, Michelle
Supervisor and department
Treit, Dallas (Psychology, Neuroscience)
Examining committee member and department
Dickson, Clayton (Psychology, Neuroscience, Physiology)
Dringenberg, Hans (Psychology)
Hurd, Pete (Psychology)
Baker, Glen (Psychiatry)
Sturdy, Chris (Psychology)
Department of Psychology

Date accepted
Graduation date
Doctor of Philosophy
Degree level
Despite considerable research progress towards characterizing the neurobiology of anxiety, the focus on putative behavioral markers and the absence of a common behavioural/neurobiological signature for the different classes of anxiolytic drugs have potentially slowed research into the neural mechanisms of anxiolytic drug action. As such, current research efforts are dedicated towards identifying neural indices that yield universal signatures across all anxiolytic compounds. This, in turn, may facilitate the development of therapeutics for clinical anxiety disorders. The general purpose of this thesis is to identify and characterize putative compounds with anxiolytic potential and to critically evaluate an emerging neurophysiological model of anxiolytic drug action. Chapter 1 of this thesis will provide a systematic overview of current animal behavioral models of anxiety, summarize the role of several neurotransmitter systems in the biochemical basis of anxiety, describe the seminal work characterizing the neuroanatomical correlates of anxiety, characterize the role of hippocampal theta in the neurobiology of anxiety, and identify novel pharmacological targets. In chapter 2, the anxiolytic properties of somatostatin following intra-amygdala and intra-septal microinfusions and the receptor specificity of these effects will be summarized. Here, we found that a selective sst2 receptor antagonist, PRL2903 can reverse the anxiolytic effects of somatostatin in two well established behavioral models of anxiety, the elevated plus-maze and shock probe burying test. Chapter 3 will provide a critical assessment of the hippocampal theta suppression model of anxiolytic drug action. Here, we found that the bradycardic agent ZD7288 significantly suppresses reticularly activated theta frequency and produces corresponding anxiolytic effects in the elevated plus-maze. In chapter 4, three well established anxiogenic agents FG7142, yohimbine, and βCCE will be used to assess the construct validity of the theta model, (i.e. to evaluate the functional role of theta frequency in anxiety per se). Here, we found that all three anxiogenic agents reliably produced anxiogenic-like effects in the elevated plus-maze but had no effects on theta frequency. Chapter 5 of this thesis will explore the regional and functional differences of the dorsal and ventral hippocampus in relation to the theta suppression model using histamine, an important neurotransmitter in the brain. Paradoxically, we found that histamine produced marked increases to theta frequency following ventral hippocampal microinfusions while eliciting robust anxiolytic effects in the elevated plus-maze. Finally, chapter 6 will summarize the major results and conclusions of these studies, describe their limitations and propose future directions for research on novel models and mechanisms in the neurobiology of anxiety.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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