5-HT7 receptor deletion enhances REM sleep suppression induced by selective serotonin reuptake inhibitors, but not by direct stimulation of 5-HT1A receptor |
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Authors: | Shelton Jonathan Bonaventure Pascal Li Xiaorong Yun Sujin Lovenberg Timothy Dugovic Christine |
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Affiliation: | Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Neuroscience, 3210 Merryfield Row, San Diego, CA 92121, USA |
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Abstract: | 5-HT7 receptors are involved in REM sleep and possibly in mood disorders. REM sleep suppression and antidepressant-like behavior is observed in 5-HT7−/− mice and in rats treated with 5-HT7 receptor antagonists. We recently demonstrated that pharmacological blockade of 5-HT7 receptors enhances REM sleep suppression and antidepressant-like behavior induced by citalopram in rodents. It has been hypothesized that the effect of citalopram on sleep is essentially mediated by the activation of 5-HT1A receptors. The present study investigates the impact of 5-HT7 receptor gene deletion on the effect of various reuptake inhibitors on REM sleep and probes the role of 5-HT1A receptors in this response. Three SSRIs (citalopram, fluoxetine and paroxetine) but not the tricyclic antidepressant desipramine had a significantly stronger REM sleep suppressive effect in 5-HT7−/− mice compared to 5-HT7+/+ mice. In contrast, REM sleep was similarly reduced in 5-HT7+/+ mice and 5-HT7−/− mice after treatment with the 5-HT1A receptor agonist ipsapirone. Furthermore, both 5-HT7+/+ and 5-HT7−/− mice displayed the same increase in REM sleep duration produced by the 5-HT1A receptor antagonist WAY-100635. These findings indicate that 5-HT7 receptor deletion augments the effect of various SSRIs on REM sleep suppression and that this effect is distinct from those mediated via 5-HT1A receptors. |
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Keywords: | REM sleep 5-HT7 receptor SSRI Depression 5-HT1A receptor |
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