Anxiety disorders are the most prevalent of all psychiatric conditions. However, current pharmacological treatments for anxiety disorders are characterized by one or more of the following deficiencies: 1) unwanted side effects, 2) partial efficacy, 3) addictive potential, and 4) delayed onset of therapeutic effects. These therapeutic liabilities motivate the search for better pharmacological treatments. This research effort has been concentrated in three broad, neuropharmacological domains: 1) Sub-unit specific GABAA receptor agonists, 2) Neurosteroids, and 3) Neuropeptides. The general purpose of this thesis was to advance our understanding of the putative anxiolytic potential of neurosteroids and neuropeptides, and their neural mechanisms of action, as revealed by intracerebral infusion studies in animal models of anxiety.
Chapter 1 of this thesis will provide a systematic review of what is now known about the behavioral effects of intra-cerebrally infused agonists and antagonists of anxiolytic compounds in animal models of anxiety. A theoretical context in which to view the empirical work is also outlined. Chapter 2 will provide a brief introduction to neurosteroids and neuropeptides, and their potential as anxiolytic drugs as suggested by the current literature. In Chapter 3, the anxiolytic-like effects of the neurosteroid allopregnanolone were examined in the amygdala, the hippocampus or the medial prefrontal cortex. Allopregnanolone had site- and test-specific anxiolytic effects, causing anxiolysis following infusion into the amygdala and the medial prefrontal cortex. In Chapter 4, the anxiety-related effects of two receptor antagonists of the neuropeptide arginine vasopressin were investigated in the hippocampus. Anxiolytic effects were specific to both receptor sub-type and by infusion site. In chapter 5, the putative anxiolytic and antidepressant effects of the neuropeptide somatostatin were investigated. Intracerebroventricular microinfusion of somatostatin produced anxiolytic-like and antidepressant-like signatures in distinct domains. In chapter 6, selective agonists for each of the 5 G-protein coupled somatostatin receptors were administered to rats. Intracerebroventricular administration of an sst2 agonist produced anxiolytic-like effects, whereas an antidepressant-like effect was observed following the administration of both sst2 and sst3 agonists.
In summary, the present thesis provides important clues to the neurochemical correlates of anxiety, and its potential treatment with alternative compounds such as neuropeptides.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/790 |
| Date | 11 1900 |
| Creators | Engin, Elif |
| Contributors | Treit, Dallas (Psychology), Colbourne, Frederick (Psychology), Dickson, Clayton (Psychology), Hurd, Peter (Psychology), Todd, Kathryn (Psychiatry), Shekhar, Anantha (Psychiatry, Indiana University) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
| Format | 2237651 bytes, application/pdf |
| Relation | Engin E, Treit D (2007) The anxiolytic-like effects of allopregnanolone function of intracerebral microinfusion site: the amygdala, medial prefrontal cortex or hippocampus. Behavioral Pharmacology, 18, 461-470., Engin E, Treit D (2008) Dissociation of the anxiolytic-like effects of Avpr1a and Avpr1b receptor antagonists in the dorsal and ventral hippocampus. Neuropeptides, 42, 411-421., Engin E, Treit D (2008) The effects of intra-cerebral drug infusions on animals unconditioned fear reactions: A Systematic review. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 32, 1399-1419., Engin E, Stellbrink J, Treit D, Dickson CT (2008) Anxiolytic and antidepressant effects of intracerebroventricularly administered somatostatin: Behavioral and neurophysiological evidence. Neuroscience, 157, 666-676., Engin E, Treit D (2009) Anxiolytic and antidepressant actions of somatostatin: The role of sst2 and sst3 receptors. Psychopharmacology, 206, 281-289. |
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