Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.664024
Title: Modulation of the serotonin transporter and receptors by antidepressants and ecstasy
Author: Wren, Paul Bryan
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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Abstract:
In this thesis the effects of chronic antidepressant treatments and MDMA treatment on the density and affinity of a variety of regional rat brain 5-HT and non-5-HT transporters and receptors is investigated using radioligand binding and immunological techniques. The influence of potentially neuroprotective drugs on the effects of MDMA is examined. Since SERT mRNA has been detected in the rat adrenal gland, the effects of antidepressant and MDMA treatment on adrenal SERT has also been determined. A novel [3H]5-CT membrane binding assay, in the presence of specific 5-HT receptor subtype masking drugs, revealed a pharmacology consistent with 5-HT7 receptor binding. The pharmacological profile of [3H]GR125, 743 membrane binding was consistent with binding to 5-HT1B/1D receptors, known to regulate 5-HT neurotransmission. Decreases in 5-HT7, 5-HT1B and 5-HT1D receptor density were observed in rat frontal neocortex after chronic SSR1, but not tianeptine (atypical antidepressant), treatment. No adaptive changes were observed for noradrenaline transporters, 5-HT1A or dopamine1 receptors. Adrenal gland SERT displayed an identical pharmacology to brain and platelet SERT and was also unaffected by such treatments. A library of site directed antibodies raised against SERT were characterised. A monoclonal antibody which specifically recognised denatured SERT and displayed the appropriate immunohistochemical labelling, also immunoprecipitated SERT and specifically recognised the native form from rat cortex and platelets. SERT protein was specifically detected in the rat adrenal medulla by this antibody. MDMA exposure caused a similar depletion in the number of SERT binding sites in both the brain and adrenal gland. GK506 protected brain neurotoxicity, but did not protect adrenal SERT depletion. The MDMA SERT reduction was still apparent after 13 weeks in the brain, but not in the adrenal glands. In the brain, MDMA neurotoxicity was also rescued by a free radical scavenger.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.664024  DOI: Not available
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