Role of 5-HT6 receptor in conditioned learning and memory
The recently discovered 5-HT6 receptor has generated interest due to increasing evidence for its role in feeding, obesity, anxiety, depression and cognition. Initial studies utilising selective 5-HT6 receptor antagonists found pro-cognitive effects in various cognitive paradigms. In the last three...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
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2011
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| Online Access: | https://eprints.nottingham.ac.uk/11939/ |
| _version_ | 1848791393871331328 |
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| author | Woods, Susie |
| author_facet | Woods, Susie |
| author_sort | Woods, Susie |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | The recently discovered 5-HT6 receptor has generated interest due to increasing evidence for its role in feeding, obesity, anxiety, depression and cognition. Initial studies utilising selective 5-HT6 receptor antagonists found pro-cognitive effects in various cognitive paradigms. In the last three years selective 5-HT6 receptor agonists have been developed and initial reports suggested they impaired cognition as predicted, but more recent reports have found paradoxical pro-cognitive effects in learning and memory tasks. The main aim of the current thesis was to determine the role of the 5-HT6 receptor in a conditioned emotion response (CER) task in rats. Both the effects of 5-HT6 receptor antagonists and agonists given alone, and their abilities to reverse a cholinergic- or glutamatergic-induced memory impairment were analysed. Secondly, to analyse the intracellular mechanisms involved in the behavioural effects exerted following treatment with 5-HT6 receptor ligands by examining changes in hippocampal protein expression.
Pre-treatment with either the muscarinic receptor antagonist, scopolamine, or the NMDA receptor antagonist, MK-801, induced memory impairment in the 24 hour retention trial. Post-training administration of 5-HT6 receptor antagonist, SB-271046, and agonists, EMD 386088 and E-6801, had little effect on CER-induced behaviour when given alone, but both reversed the cholinergic- and glutamatergic-induced deficits.
Western blot analysis revealed no significant difference between hippocampal BDNF and 5-HT6 receptor protein levels following any drug or shock treatment, but some interesting trends were observed. CER slightly increased BDNF expression, this was reduced by scopolamine and MK-801 which in turn was reversed with SB-271046 and EMD 386088. CER decreased 5-HT6 receptor expression, scopolamine caused further reduction, SB-271046 and EMD 386088 increased the expression following scopolamine. MK-801 increased 5-HT6 receptor expression, whilst SB-271046 further enhanced this expression, EMD 386088 reduced it. No significant results were observed in the proteomic studies.
These findings provide further evidence for the exciting potential therapeutic use of 5-HT6 receptor compounds in the treatment of cognitive dysfunction. |
| first_indexed | 2025-11-14T18:27:48Z |
| format | Thesis (University of Nottingham only) |
| id | nottingham-11939 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T18:27:48Z |
| publishDate | 2011 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-119392025-02-28T11:16:36Z https://eprints.nottingham.ac.uk/11939/ Role of 5-HT6 receptor in conditioned learning and memory Woods, Susie The recently discovered 5-HT6 receptor has generated interest due to increasing evidence for its role in feeding, obesity, anxiety, depression and cognition. Initial studies utilising selective 5-HT6 receptor antagonists found pro-cognitive effects in various cognitive paradigms. In the last three years selective 5-HT6 receptor agonists have been developed and initial reports suggested they impaired cognition as predicted, but more recent reports have found paradoxical pro-cognitive effects in learning and memory tasks. The main aim of the current thesis was to determine the role of the 5-HT6 receptor in a conditioned emotion response (CER) task in rats. Both the effects of 5-HT6 receptor antagonists and agonists given alone, and their abilities to reverse a cholinergic- or glutamatergic-induced memory impairment were analysed. Secondly, to analyse the intracellular mechanisms involved in the behavioural effects exerted following treatment with 5-HT6 receptor ligands by examining changes in hippocampal protein expression. Pre-treatment with either the muscarinic receptor antagonist, scopolamine, or the NMDA receptor antagonist, MK-801, induced memory impairment in the 24 hour retention trial. Post-training administration of 5-HT6 receptor antagonist, SB-271046, and agonists, EMD 386088 and E-6801, had little effect on CER-induced behaviour when given alone, but both reversed the cholinergic- and glutamatergic-induced deficits. Western blot analysis revealed no significant difference between hippocampal BDNF and 5-HT6 receptor protein levels following any drug or shock treatment, but some interesting trends were observed. CER slightly increased BDNF expression, this was reduced by scopolamine and MK-801 which in turn was reversed with SB-271046 and EMD 386088. CER decreased 5-HT6 receptor expression, scopolamine caused further reduction, SB-271046 and EMD 386088 increased the expression following scopolamine. MK-801 increased 5-HT6 receptor expression, whilst SB-271046 further enhanced this expression, EMD 386088 reduced it. No significant results were observed in the proteomic studies. These findings provide further evidence for the exciting potential therapeutic use of 5-HT6 receptor compounds in the treatment of cognitive dysfunction. 2011-07-15 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/11939/1/Thesis_S_Woods.pdf Woods, Susie (2011) Role of 5-HT6 receptor in conditioned learning and memory. PhD thesis, University of Nottingham. 5-h56 receptor serotonin conditioned learning memory cognition conditioned emotion response |
| spellingShingle | 5-h56 receptor serotonin conditioned learning memory cognition conditioned emotion response Woods, Susie Role of 5-HT6 receptor in conditioned learning and memory |
| title | Role of 5-HT6 receptor in conditioned learning and memory |
| title_full | Role of 5-HT6 receptor in conditioned learning and memory |
| title_fullStr | Role of 5-HT6 receptor in conditioned learning and memory |
| title_full_unstemmed | Role of 5-HT6 receptor in conditioned learning and memory |
| title_short | Role of 5-HT6 receptor in conditioned learning and memory |
| title_sort | role of 5-ht6 receptor in conditioned learning and memory |
| topic | 5-h56 receptor serotonin conditioned learning memory cognition conditioned emotion response |
| url | https://eprints.nottingham.ac.uk/11939/ |