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Title: Hormonal effects on brain 5-HT function
Author: Young, A. H.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1996
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The purpose of the work carried out in this thesis was to examine hormonal effects on central nervous system serotonergic (5-hydroxtryptamine; 5-HT) receptor function. Experiments were carried out using established rodent (mouse and rat) models of central 5-HT receptor function. Corticosteroids were administered, both acutely and chronically, and the effects on these models assessed. Corticosteroids were found to have relatively selective effects: in the mouse and rat certain models of 5-HT1A receptor function were attenuated and in the mouse corticosteroids enhanced behavioural models of 5-HT release. No effects were found on models of other central 5-HT receptor functions. These effects were found to be both time and dose dependent and to reverse after the administration of corticosteroids ceased. Removal of endogenous corticosteroids, by adrenalectomy, was found to cause an enhancement of 5-HT1A receptor function. A sex difference, in rodents, in 5-HT1A receptor function was found which was abolished by ovariectomy. The action of corticosterone in producing these effects could not be replicated by selective corticosteroid receptor antagonists. Further experiments were carried out in healthy human male volunteers. Buspirone was shown to induce a hypothermic response significantly greater than placebo. The effects of hydrocortisone administration (20mg, orally, twice daily) on the sensitivity of brain 5-HT1A receptors in healthy volunteers were then studied using a buspirone challenge paradigm. These experiments show that the effects of corticosteroids are relatively selective to 5-HT1A receptors. The effect of corticosteroids on 5-HT1A receptors may be the mechanism whereby exogenous corticosteroids affect mood. Furthermore, the effects of endogenous corticosteroids on 5-HT receptor function may be important in the pathophysiology of mood disorders.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available