Several lines of evidence suggest an involvement of serotonin$ sb{ rm 1A}$ (5-HT$ sb{ rm 1A}$ receptors in the regulation of emotions. In order to investigate the molecular basis of recent electrophysiological findings which implicated 5-HT$ sb{ rm 1A}$ receptors in the mechanism of action of antidepressants and anxiolytics, radioligand binding and autoradiographic studies using tritiated 8-hydroxy-2-(di-N-propylamino)-tetralin ( ($ sp3$H) -8-OH-DPAT) were done in rat brain following various treatments. These included: the tricyclic antidepressant imipramine; the reuptake blockers paroxetine and indalpine; the monoamine oxidase inhibitor clorgyline; electroconvulsive shock; lithium; the classic benzodiazepine diazepam; and the 5-HT$ sb{ rm 1A}$ partial agonist gepirone. None of these treatments, nor the fluctuation in 5-HT availability provoked by the circadian cycle, gave any significant changes, with the exception of clorgyline which initially appeared to decrease the affinity of ($ sp3$H) -8-OH-DPAT for its receptor. A further series of studies in vitro and in vivo ascertained the possibility that the 5-HT$ sb{ rm 1A}$ receptors may display two interconvertible affinity states and that, in fact, clorgyline induces a shift of the high to the lower affinity state. The findings from this second series of experiments suggested that labile changes, which may possibly be disrupted during membrane preparation, in the coupling between the 5-HT$ sb{ rm 1A}$ receptor and a guanine nucleotide binding protein (G-protein) may account for the effects that certain treatments have on 5-HT$ sb{ rm 1A}$ receptor responsiveness.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.59934 |
| Date | January 1990 |
| Creators | Mongeau, Raymond |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Psychiatry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001213404, proquestno: AAIMM67502, Theses scanned by UMI/ProQuest. |
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