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Title: Neurotransmitter regulated neuronal gene expression : a role for cholecystokinin
Author: Brown, P.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1997
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The aim of this study was to examine cholecystokinin-induced neuronal stimulation, using gene expression as an index of neuronal activation. The initial experiments were designed to establish whether endogenous cholecystokinin utilised the same CCK-A pathway as peripherally administered cholecystokinin. By manipulating the cholecystokinin-receptor pathway, using devazepide (CCK-A receptor antagonist) and bilateral subdiaphragmatic vagotomy, it was shown that CCK-8 released during feeding utilised the same CCK-A receptors on vagal afferents, as systemically administered CCK-8, and induced immediate early gene (IEG) mRNA expression in the same brainstem and hypothalamic nuclei. Therefore, cholecystokinin acted as a transmitter in the central nervous system, inducing specific neuronal activation. The second series of experiments examined the role of cholecystokinin and other neurotransmitters in anxiety and stress. Gene expression was utilised as a index of neuronal activity following stress. As CCK-B receptor antagonists produced anxiolytic responses in ethological models of anxiety, I examined whether IEG mRNA expression during stress was linked to the central release of CCK. The results of these experiments showed that IEG expression during exposure to the elevated plusmaze was mainly associated with the release of noradrenaline, while CCK-B receptors were involved in the IEG response to social defeat stress. Therefore stress-specific activation of (1) CCK-B receptors and (2) IEG mRNA expression was observed, suggesting that a common stress pathway does not exist, with the IEG mRNA response being model or stress specific. In addition, the IEG mRNA response to repeated elevated plusmaze stress did not habituate during chronic stress, and remained at the same high level of expression in the same brain regions, as seen following a single exposure to the maze.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available