5-HT7 receptor deletion enhances REM sleep suppression induced by selective serotonin reuptake inhibitors, but not by direct stimulation of 5-HT1A receptor
Copyright policy )5-HT7 receptor deletion enhances REM sleep suppression induced by selective serotonin reuptake inhibitors, but not by direct stimulation of 5-HT1A receptor
5-HT(7) receptors are involved in REM sleep and possibly in mood disorders. REM sleep suppression and antidepressant-like behavior is observed in 5-HT(7)(-/-) mice and in rats treated with 5-HT(7) receptor antagonists. We recently demonstrated that pharmacological blockade of 5-HT(7) 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-HT(1A) receptors. The present study investigates the impact of 5-HT(7) receptor gene deletion on the effect of various reuptake inhibitors on REM sleep and probes the role of 5-HT(1A) 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-HT(7)(-/-) mice compared to 5-HT(7)(+/+) mice. In contrast, REM sleep was similarly reduced in 5-HT(7)(+/+) mice and 5-HT(7)(-/-) mice after treatment with the 5-HT(1A) receptor agonist ipsapirone. Furthermore, both 5-HT(7)(+/+) and 5-HT(7)(-/-) mice displayed the same increase in REM sleep duration produced by the 5-HT(1A) receptor antagonist WAY-100635. These findings indicate that 5-HT(7) receptor deletion augments the effect of various SSRIs on REM sleep suppression and that this effect is distinct from those mediated via 5-HT(1A) receptors.
- Johnson & Johnson Pharmaceutical Research and Development China (People's Republic of)
- Johnson & Johnson (United States) United States
Mice, Knockout, Analysis of Variance, Time Factors, Sleep, REM, Electroencephalography, Serotonin Receptor Agonists, Mice, Inbred C57BL, Mice, Pyrimidines, Receptors, Serotonin, Receptor, Serotonin, 5-HT1A, Reaction Time, Animals, Serotonin Antagonists, Selective Serotonin Reuptake Inhibitors
Mice, Knockout, Analysis of Variance, Time Factors, Sleep, REM, Electroencephalography, Serotonin Receptor Agonists, Mice, Inbred C57BL, Mice, Pyrimidines, Receptors, Serotonin, Receptor, Serotonin, 5-HT1A, Reaction Time, Animals, Serotonin Antagonists, Selective Serotonin Reuptake Inhibitors
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