title: Effects of serotonergic agents on respiratory recovery after cervical spinal injury.
abstract: Unilateral cervical spinal cord hemisection (i.e., C2Hx) usually interrupts the bulbospinal respiratory pathways and results in respiratory impairment. It has been demonstrated that activation of the serotonin system can promote locomotor recovery after spinal cord injury. The present study was designed to investigate whether serotonergic activation can improve respiratory function during the chronic injury state. Bilateral diaphragm electromyogram and tidal volume were measured in anesthetized and spontaneously breathing adult rats at 8 wk post-C2Hx or C2 laminectomy. A bolus intravenous injection of a serotonin precursor [5-hydroxytryptophan (5-HTP), 10 mg/kg], a serotonin reuptake inhibitor (fluoxetine, 10 mg/kg), or a potent agonist for serotonin 2A receptors (TCB-2, 0.05 mg/kg) was used to activate the serotonergic system. Present results demonstrated that 5-HTP and TCB-2, but not fluoxetine, significantly increased the inspiratory activity of the diaphragm electromyogram ipsilateral to the lesion for at least 30 min in C2Hx animals, but not in animals that received sham surgery. However, the tidal volume was not increased after administration of 5-HTP or TCB-2, indicating that the enhancement of ipsilateral diaphragm activity is not associated with improvement of the tidal volume. These results suggest that exogenous activation of the serotonergic system can specifically enhance the ipsilateral diaphragmatic motor outputs, but this approach may not be sufficient to improve respiratory functional recovery following chronic cervical spinal injury.
authors.affiliation: Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan;
authors.forename: Shih-Hui
authors.initials: SH
authors.lastname: Hsu
authors.affiliation: Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Center for Neuroscience, National Sun Yat-sen University, Kaohsiung, Taiwan; Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; and Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung, Taiwan kzlee@mail.nsysu.edu.tw.
authors.forename: Kun-Ze
authors.initials: KZ
authors.lastname: Lee
mesh_terms: D000818:Animals; D002574:Cervical Vertebrae / Q000293:injuries*; D003964:Diaphragm / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology; D018490:Serotonin Agents / Q000494:pharmacology / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D013990:Tidal Volume / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D018490:Serotonin Agents
keywords: cervical spinal cord injury; diaphragm; respiration; serotonin