Effects of serotonin on crossed phrenic nerve activity in cervical spinal cord hemisected rats

The present study investigates the effect of 5-hydroxytryptophan (5-HTP), a serotonin precursor, on crossed phrenic nerve activity (CPNA) in rats subjected to a left C2 spinal cord hemisection. Electrophysiological experiments were conducted on anesthetized, vagotomized, paralyzed, and artificially ventilated rats to assess phrenic nerve activity. The left phrenic nerve lost rhythmic activity due to the disruption of the bulbospinal respiratory pathways following spinal cord hemisection. Activity was induced in the left phrenic nerve (CPNA) by temporary asphyxia. 5-HTP administration increased CPNA during asphyxia in the left phrenic nerve in a dose-dependent fashion. Specifically, in a group of eight animals, application of 5-HTP at 0.5, 1.0, and 2.0 mg/kg significantly increased CPNA by 102.2+/-18.5%, 200.8+/-58.1%, and 615.0+/-356.9% compared with predrug control values, respectively. 5-HTP-induced increases in CPNA were reversed by methysergide (2-6 mg/kg, i.v.), a serotonin receptor antagonist. The results suggest that serotonin is involved in the modulation of crossed phrenic nerve activity following spinal cord injury.