QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, December 7, 2005, 25(49):11231-11238; doi:10.1523/JNEUROSCI.1724-05.2005

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (30) Citing Articles via Google Scholar Google Scholar Articles by Popa, D. Articles by Adrien, J. Search for Related Content PubMed PubMed Citation Articles by Popa, D. Articles by Adrien, J.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Contribution of 5-HT₂ Receptor Subtypes to Sleep–Wakefulness and Respiratory Control, and Functional Adaptations in Knock-Out Mice Lacking 5-HT_2A Receptors

Daniela Popa,¹ Clément Léna,⁴ Véronique Fabre,¹ Caroline Prenat,² Jay Gingrich,³ Pierre Escourrou,² Michel Hamon,¹ and Joëlle Adrien¹

¹Unité Mixte de Recherche 677, Institut National de la Santé et de la Recherche Médicale/Universite Pierre et Marie Curie, 75013 Paris, France, ²Équipe Associée 3544, Institut Fédératif de Recherche–Institut de Signalisation et Innovation Thérapeutique, 92296 Chatenay-Malabry, France, ³Department of Psychiatry, Columbia University, New York, New York 10032, and ⁴Unité Mixte de Recherche 8544, École Normale Supérieure, 75005 Paris, France

Serotonin (5-hydroxytryptamine; 5-HT) plays key roles in sleep–wakefulness regulation. Evidence indicates that 5-HT₂ receptors are involved mainly in non-rapid eye movement sleep (NREMS) regulation and respiratory control. Here, we investigated the relative contribution of 5-HT_2A, 5-HT_2B, and 5-HT_2C receptor subtypes to NREMS and breathing during sleep, using 5-HT₂ subtype-selective ligands in wild-type (5-HT_2A+/+) and knock-out (5-HT_2A–/–) mice that do not express 5-HT_2A receptors. Acute blockade of 5-HT_2A receptors induced an increase in NREMS in 5-HT_2A+/+ mice, but not 5-HT_2A–/– mutants, which spontaneously expressed less NREMS than wild-type animals. In 5-HT_2A+/+ mice, 5-HT_2B receptor blockade produced a reduction of NREMS, whereas receptor activation induced an increase in this sleep stage. These effects were less pronounced in 5-HT_2A–/– mice, indicating a lower sensitivity of 5-HT_2B receptors in mutants, with no change in 5-HT_2B mRNA. Blockade of 5-HT_2C receptors had no effect on NREMS in both strains. In addition, an increase in EEG power density after sleep deprivation was observed in 5-HT_2A+/+ mice but not in 5-HT_2A–/– mice. Whole-body plethysmographic recordings indicated that 5-HT_2A receptor blockade in 5-HT_2A+/+ mice reduced NREMS apneas and bradypneas that occurred after sighs. In contrast, in 5-HT_2A–/– mutants, NREMS apneas were not modified, and bradypnea after sighs were more pronounced. Our results demonstrate that 5-HT exerts a 5-HT_2B-mediated facilitation of NREMS, and an influence respectively inhibitory on NREMS and facilitatory on sleep apnea generation, via 5-HT_2A receptors. Moreover, 5-HT_2A gene knock-out leads to functional compensations yielding adaptive changes opposite to those caused by pharmacological blockade of 5-HT_2A receptors in 5-HT_2A+/+ mice.

Key words: serotonin; sleep; mice; 5-HT₂ receptors; sleep deprivation; apnea; respiration; serotonergic; depression; knock-out mice; EEG

---

Received April 29, 2005; revised October 6, 2005; accepted October 7, 2005.

This article has been cited by other articles:

				L. Paterson, S. Wilson, D. Nutt, P. Hutson, and M Ivarsson Characterisation of the effects of caffeine on sleep in the rat: a potential model of sleep disruption J Psychopharmacol, July 1, 2009; 23(5): 475 - 486. [Abstract] [PDF]

				C. Gaultier and J Gallego Neural control of breathing: insights from genetic mouse models J Appl Physiol, May 1, 2008; 104(5): 1522 - 1530. [Abstract] [Full Text] [PDF]

				D. Popa, C. Lena, C. Alexandre, and J. Adrien Lasting Syndrome of Depression Produced by Reduction in Serotonin Uptake during Postnatal Development: Evidence from Sleep, Stress, and Behavior J. Neurosci., April 2, 2008; 28(14): 3546 - 3554. [Abstract] [Full Text] [PDF]

				S. Doly, E. Valjent, V. Setola, J. Callebert, D. Herve, J.-M. Launay, and L. Maroteaux Serotonin 5-HT2B Receptors Are Required for 3,4-Methylenedioxymethamphetamine-Induced Hyperlocomotion and 5-HT Release In Vivo and In Vitro J. Neurosci., March 12, 2008; 28(11): 2933 - 2940. [Abstract] [Full Text] [PDF]

				S. Zanella, F. Watrin, S. Mebarek, F. Marly, M. Roussel, C. Gire, G. Diene, M. Tauber, F. Muscatelli, and G. Hilaire Necdin Plays a Role in the Serotonergic Modulation of the Mouse Respiratory Network: Implication for Prader-Willi Syndrome J. Neurosci., February 13, 2008; 28(7): 1745 - 1755. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help