The aim of the present study was to specifically investigate the involvement of serotonin [5-hydroxytryptamine (5-HT2)] receptors in 5-HT-mediated respiratory recovery after cervical hemisection. Experiments were conducted on C2 spinal cord-hemisected, anesthetized (chloral hydrate, 400 mg/kg ip), vagotomized, pancuronium- paralyzed, and artificially ventilated female Sprague-Dawley rats in which CO2 levels were monitored and maintained. Twenty-four hours after spinal hemisection, the ipsilateral phrenic nerve displayed no respiratory-related activity indicative of a functionally complete hemisection. Intravenous administration of the 5-HT2A/2C-receptor agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) induced respiratory-related activity in the phrenic nerve ipsilateral to hemisection under conditions in which CO2 was maintained at constant levels and augmented the activity induced under conditions of hypercapnia. The effects of DOI were found to be dose dependent, and the recovery of activity could be maintained for up to 2 h after a single injection. DOI-induced recovery was attenuated by the 5-HT2-receptor antagonist ketanserin but not with the 5-HT2C-receptor antagonist RS-102221, suggesting that 5-HT2A and not necessarily 5-HT2C receptors may be involved in the induction of respiratory recovery after cervical spinal cord injury.
Phrenic Motor Neuron Survival Below a Cervical Spinal Cord Injury
