Serotonin(2) receptors mediate respiratory recovery after cervical spinal cord hemisection in adult rats

The aim of the present study was to specifically investigate the involvemen t of serotonin [5-hydroxytryptamine (5-HT2)] receptors in 5-HT-mediated res piratory recovery after cervical hemisection. Experiments were conducted on C-2 spinal cord-hemisected, anesthetized (chloral hydrate, 400 mg/kg ip), vagotomized, pancuronium-paralyzed, and artificially ventilated female Spra gue-Dawley rats in which CO2 levels were monitored and maintained. Twenty-f our hours after spinal hemisection, the ipsilateral phrenic nerve displayed no respiratory-related activity indicative of a functionally complete hemi section. Intravenous administration of the 5-HT2A/2C-receptor agonist (+/-) -2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) induced respiratory-re lated activity in the phrenic nerve ipsilateral to hemisection under condit ions in which CO2 was maintained at constant levels and augmented the activ ity 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 a ntagonist RS-102221, suggesting that 5-HT2A and not necessarily 5-HT2C rece ptors may be involved in the induction of respiratory recovery after cervic al spinal cord injury.