Effects of the serotonin synthesis inhibitor p-CPA on the expression of the crossed phrenic phenomenon 4 h following C2 spinal cord hemisection.

Abstract

The present study assesses the effects of para-chlorophenylalanine (p-CPA), a serotonin-depleting drug, on the recovery of respiratory-related activity in the phrenic nerve induced by asphyxia 4 h following ipsilateral C2 hemisection in young adult rats. HPLC analysis was used to quantify levels of serotonin (5-HT), dopamine (DA), norepinephrine, and the 5-HT metabolite, 5-hydroxyindoleacetic acid, in the C4 segment of the spinal cord, all of which were significantly lower in p-CPA-treated hemisected rats compared to hemisected controls receiving saline. Hemisection alone was found to significantly increase 5-HT levels and significantly decrease DA levels compared to normal controls. Eight of eight saline-injected rats expressed recovery of respiratory-related activity in the ipsilateral phrenic nerve during asphyxia 4 h following hemisection, while only 4/8 rats in the p-CPA-treated group expressed recovery in the ipsilateral nerve. Quantification of integrated phrenic nerve wave-forms indicated that the mean amplitude of respiratory-related activity in the ipsilateral phrenic nerve was significantly lower in p-CPA-treated rats than in saline controls. In addition, saline controls demonstrated significant increases in mean respiratory frequency and mean amplitude of contralateral phrenic nerve activity during asphyxia, compared to normocapnia. However, p-CPA-treated rats did not express significant differences in either mean respiratory frequency or mean amplitude of integrated respiratory wave-forms during asphyxia, compared to normocapnia. The results suggest that p-CPA treatment attenuates the recovery of respiratory-related activity in the phrenic nerve 4 h following ipsilateral C2 hemisection and attenuates asphyxia-induced increases in respiratory frequency and respiratory burst amplitude recorded from the contralateral phrenic nerve.