Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.661304
Title: An investigation into the actions of 5-HT as revealed by WAY-100635 in the rat DRN
Author: Robinson, Sharon Marie
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
Abstract:
Intracellular recordings were made from presumptive serotonergic neurones in the in vitro slice preparation of the rat dorsal raphe nucleus. The modulation of excitability of presumptive serotonergic neurones by 5-HT was investigated. Confirming previous observations bath-application of 5-HT led to a membrane hyperpolarisation with an associated decrease in input resistance. The reversal level was approximately - 90 mV, a value close to that predicted for a potassium-mediated event. The 5-HT-evoked hyperpolarisation was blocked by WAY-100635, a result consistent with the response being mediated by the 5-HT1A receptor subtype. WAY-100635 alone was found to have no effect on membrane potential or input resistance in this study and in this sense is silent. The blockade of the 5-HT1A-evoked hyperpolarisation with WAY-100635 revealed a 5-HT-evoked depolarisation associated with an increase in cell excitability. In the majority of cells tested there was no significant change in input resistance and I/V analysis failed to show a point of intersection in the range -120mV to -60mV. However, some cells did show a change in input resistance and a point of intersection could be observed at approximately -50mV. The depolarising response was observed in the presence of TTX showing it to be independent of propagated action potentials and thus unlikely to involve network synaptic events. In the present of WAY-100635 the 5-HT2 agonist DOI evoked a depolarisation with similar properties to that evoked by 5-HT. The more selective 5-HT2B/2C agonist mCPP and the 5-HT1B agonist CP 93129 had no effect in WAY-100635 treated cells. The broad spectrum 5-HT receptor antagonist methysergide blocked the 5-HT-evoked depolarisation in 6 of 8 cells as well as the depolarising action of DOI. The 5-HT2 antagonist ketanserin completely blocked the 5-HT-evoked depolarisation, as did the 5-HT2A selective antagonist MDL 100927.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.661304  DOI: Not available
Share: