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Published ahead of print on August 22, 2002, doi:10.1164/rccm.200202-107OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 4, February 2003, 563-569

A more recent version of this article appeared on February 15, 2003
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Submitted on February 12, 2002
Accepted on August 16, 2002

Pharmacological Characterization of Serotonergic Receptor Activity in the Hypoglossal Nucleus

Sigrid C Veasey1* and Polina Fenik1

1 Medicine/Sleep Div, University of PA, Philadelphia, PA, USA

* To whom correspondence should be addressed. E-mail: veasey{at}mail.med.upenn.edu.

State-dependent reductions in serotonin delivery to upper airway dilator motoneuron activity may contribute to sleep apnea. The functional significance of serotonin receptor subtypes implicated in excitation of dilator motor neurons was evaluated in anesthetized, paralyzed, mechanically-ventilated adult rats (n=108). Effects of antagonists selective for serotonin receptor subtypes 2A, 2C or 7, on intrinsic hypoglossal activity and on serotonin agonist (serotonin, 5-carboxamidotryptamine maleate, and RO-60,0175) dose-responses were characterized. All drugs were injected unilaterally into the hypoglossal nucleus. The 2A-antagonist, MDL-100,907, dropped intrinsic hypoglossal nerve respiratory activity by 61%±6, p<0.001) and suppressed serotonin excitation of hypoglossal nerve activity, p<0.05. The 2C-antagonist, SB-242,084, dropped hypoglossal nerve activity 17%±6, p<0.05 and suppressed the dose-response curve for the 2C-agonist. Rapid desensitization occurred with the 2C-agonist only (p<0.05). The 7-antagonist, SB-269,970, had no effect on either intrinsic activity or agonist responses. We conclude that serotonin 2A is the predominant excitatory serotonin receptor subtype at hypoglossal motor neurons. The serotonin 2C excitatory effects are of lower magnitude and associated with rapid desensitization. There is no evidence for serotonin 7 activity in the hypoglossal nucleus. This characterization of serotonin receptor subtypes in the hypoglossal nucleus provides a focus for the development of pharmacotherapies for sleep apnea.
Key words: motor neurons, respiratory, serotonin, microinjection, obstructive sleep apnea




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