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Title: Analysis of the role of the central nociceptin system in stress
Author: Dawe, Karen
ISNI:       0000 0001 3418 1354
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2007
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Lipopolysaccharide (LPS), an immunological stressor, was found to activate the HPA axis and increase mRNA expression of the nociceptin precursor pre-pronociceptin (ppNOC) in the hypothalamus, while decreasing NOP receptor mRNA in lateral forebrain. Conversely following restraint stress, a predominantly psychological stressor, HPA axis activity was at baseline at 2- and 4-hours post stress-onset. Restraint stress reduced ppNOC mRNA in the hippocampus at 2 hours post-stress-onset, and in mediodorsal forebrain at 4 hours post-stress-onset, while reducing NOP receptor mRNA in hypothalamus at 2-hours post-stress onset, and in the medio-dorsal forebrain and hippocampal region at the 4 hour time point. Attempts were made to extend these findings to expression of NOP receptor protein, however rigorous validation experiments demonstrated that commercially available antibodies to the NOP receptor protein labelled an unknown antigen in a non-specific manner. Therefore single-unit extracellular recordings were undertaken to investigate the functional properties of nociceptin in the neural system involved in the stress response. Within the bed nucleus of the stria terminalis (BNST), extracellular single-unit recording established 4 neuronal cell-types that were distinguishable by their firing patterns. Nociceptin was found to inhibit around half of all BNST neurones. Within the ventral region of the BNST pre-treatment with physiologically relevant levels of corticosterone dramatically reduced the likelihood that neurones would be inhibited by application of nociceptin. However, exposure to restraint stress had no effect on the likelihood that neurones would display an inhibitory response to nociceptin. Thus the inhibitory action of nociceptin may differ according to whether or not the HPA axis has previously been activated, possibly via changes in NOP receptor mRNA expression. This is consistent with the proposed role of nociceptin in the termination of the HPA axis response, a notion that is further supported by preliminary in vivo experiments presented in this thesis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available