Effects of a κ-receptor agonist U-50488 on bulbar respiratory neurons and its antagonistic action against the μ receptor-induced respiratory depression in decerebrate cats

The function of ic receptor-mechanisms in bulbar respiratory network was investigated in decerebrate cats. Intravenous injection of U-50488 (0.3-3.0 mg/kg) dose-dependently decreased the phrenic nerve discharge and shortened inspiration and expiration. U-50488 caused hyperpolarization, and decreased input resistance and the action potential discharge in respiratory neurons. The effects of U-50488 were antagonized by nor-binaltorphimine. DAMGO (0.3 mg/kg, i.v.) decreased the phrenic discharge and prolonged inspiration and expiration. U-50488 partially reversed the respiratory depression induced by DAMGO. These results suggest that the activation of ic receptors by itself depresses the central respiratory activity, while it opposes the mu receptor-mediated respiratory depression.