Serotonin (5-HT) has long been implicated in the pathophysiology of depression and anxiety, and the therapeutic effect of treatments. Several drugs useful in treatment produce either acute or neuroadaptive changes in 5-HT<sub>2C</sub> receptor activity, and there has been growing interest in how alterations in the 5-HT<sub>2C</sub> receptor might be important in mediating antidepressant and anxiolytic activity. The neuropsychological hypothesis of drug action implies that the clinical effects of medications active in anxiety and depression are best understood through the effects of these agents on the processing of emotional information. Thus far, however, there has been no systematic attempt to identify the role of the 5-HT<sub>2C</sub> receptor in drug-induced changes in emotional processing in humans. The current research therefore investigated the effects of drug treatments with 5-HT<sub>2C</sub> blocking properties on neural and behavioural responses to emotional information in healthy volunteers. An fMRI study demonstrated that a single dose of mirtazapine, an antidepressant with action at the 5-HT<sub>2C</sub> receptor, reduces activation in regions important in emotional processing, such as the amygdala and the fusiform gyrus, to threat-relevant stimuli. A series of behavioural studies utilized drugs acting, at least in part, as 5-HT<sub>2C</sub> antagonists and agonists to show that these drugs are able to alter emotional processing, particularly emotional memory. A seven-day administration of mirtazapine was shown to increase the recall of positive versus negative personality characteristics. A single dose of agomelatine, also an antidepressant with putative action at the 5-HT<sub>2C</sub> receptor, did not increase slow wave sleep, suggesting, the drug had no effect of 5-HT<sub>2C</sub> blockade in the brain. In Chapter 4, agomelatine and mCPP, a 5-HT<sub>2C</sub> agonist, also shown to had no significant effect on emotional processing measures, but there was a statistical trend for agomelatine to increase memory for positive stimuli, and for mCPP to increase memory for negative stimuli. These findings suggest that antidepressants may work by altering the bias in emotional processing. Overall, the results of this exploration of the role of the 5-HT<sub>2C</sub> receptor in emotional processing have contributed to the understanding of antidepressant treatment, and raise new possibilities for the continuation of study in this field.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:556115 |
| Date | January 2010 |
| Creators | Rawlings, Nancy |
| Contributors | Harmer, Catherine |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:9bb98eb2-b753-466e-bec2-b199ad14ea34 |
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