In the feline cerebral cortex flurazepam and ethanol potenitated the inhibitory effects of iontophoretically-applied GABA and electrically-evoked inhibition (believed to be mediated by GABA). This effect is specific, since both flurazepam and ethanol antagonized the inhibitory effects of serotonin, dopamine and glycine. Moreover the degree of potentiation of GABA-mediated electrically-evoked cortical inhibition produced by five benzodiazepines (Ro 21-3981, flurazepam, chlordiazepoxide, medazepam and clozapine): (a) correlated with their relative affinities for the benzodiazepine receptor when all five drugs were applied with equal iontophoretic doses; (b) was not significantly different from one drug to another, when the benzodiazepines were applied in doses inversely proportional to their relative affinities for the benzodiazepine receptor. / Iontophoretically-applied flurazepam consistently potentiated the conductance increase produced by iontophoretically-applied GABA in CA1 and CA3 pyramidal neurons in rat hippocampus. Furthermore, both iontophoretically-applied flurazepam and intravenously injected ethanol consistently prolonged the time course of the GABA-mediated IPSP conductance increase evoked in CA1 and CA3 pyramidal hippocampal neurons by ipsilateral entorhinal or fimbrial stimulation. These effects were independent of membrane potential changes. / It is concluded that GABAergic neurotransmission has a special role in the neurophysiology of anxiety. Since anxiety is involved in the etiology of alcoholism, and since chronic ethanol intake decreases GABA levels and alters the density of GABA receptors, the results of this thesis are consistent with the hypothesis that GABAergic mechanisms may be involved in the etiology of alcoholism.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.77076 |
| Date | January 1980 |
| Creators | Nestoros, Joannis N. |
| 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 | Doctor of Philosophy (Department of Anaesthesia Research) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000102837, proquestno: AAINK52052, Theses scanned by UMI/ProQuest. |
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