Activation of 5-HT(6) receptors facilitates attentional set shifting
| العنوان: | Activation of 5-HT(6) receptors facilitates attentional set shifting |
|---|---|
| المؤلفون: | Trevor Sharp, Mark G. Baxter, Katherine E. Burnham, John R. Bainton, Eric Southam, Lee A. Dawson, David M. Bannerman |
| المصدر: | Psychopharmacology. 208(1) |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Male, Agonist, medicine.drug_class, Prefrontal Cortex, Reversal Learning, Piperazines, chemistry.chemical_compound, medicine, Animals, Attention, Receptor, Prefrontal cortex, Neurotransmitter, 5-HT receptor, Pharmacology, Sulfonamides, Behavior, Animal, Dose-Response Relationship, Drug, Cognitive flexibility, Tryptamines, Rats, Serotonin Receptor Agonists, Thiazoles, Gene Expression Regulation, chemistry, Receptors, Serotonin, Set, Psychology, Serotonin, Psychology, Immediate early gene, Neuroscience |
| الوصف: | RATIONALE: Prefrontal cortex (PFC)-dependent executive function is disrupted in a range of psychiatric disorders and can be modelled in non-human primates and rodents using attentional set-shifting paradigms. There are few current pharmacological strategies for enhancing attentional set shifting, although the PFC is rich in relevant neurotransmitter targets, including 5-hydroxytryptamine (5-HT). Although 5-HT depletion studies do not support a role for 5-HT in attentional set shifting, the effect of 5-HT activation using specific receptor agonists has not been tested. OBJECTIVES AND METHODS: This study investigated the effect of a novel, selective 5-HT(6) receptor agonist, WAY181187, in a rat model of PFC-dependent extra-dimensional (ED) attentional set shifting. The effect of this agent on immediate early gene expression in the medial PFC and other regions was also examined. RESULTS: Compared to vehicle-injected controls, WAY181187 facilitated ED set shifting but did not change other non-ED phases of the task (including intra-dimensional set shifting and reversal). This effect was blocked by the selective 5-HT(6) antagonist SB399885, which alone had no effect. WAY181187 enhanced ED set shifting even when administered after the attentional set had been acquired, thereby ruling out impairments in attentional set formation. In separate experiments, at a dose that increased ED set shifting, WAY181187 increased Fos-like immunoreactivity in the medial PFC in a SB399885-sensitive manner, suggesting a 5-HT(6) receptor-mediated activation of this region. CONCLUSIONS: Through use of a novel 5-HT agonist, these experiments reveal a previously unrecognised role for 5-HT activation in PFC-dependent executive function, mediated by 5-HT(6) receptor activation. |
| اللغة: | English |
| تدمد: | 1432-2072 0033-3158 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c918861586dc9c9486b348e2caa8feb0 http://ora.ox.ac.uk/objects/uuid:5c2b8ae1-62f2-4b03-80fd-4febabcb58a2 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c918861586dc9c9486b348e2caa8feb0 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14322072 00333158 |
|---|