OBJECTIVETo investigate the effects of doxapram on the respiratory rhythmical discharge activity (RRDA) in the brainstem slices of neonatal rats.

METHODSThirty neonatal SD rats (of either sex, 0-3 days old) were randomly divided into 6 equal groups (groups I-VI), and the brainstem slices which contained the medial region of the nucleus retrofacialis (mNRF) were prepared. All the slices were perfused with modified Kreb's solution (MKS), and in group I (control group), the slices were perfused with MKS only; in groups II to IV, the slices were perfused with doxapram in MKS continuously at the concentrations of 2, 5, and 10 micromol/L, respectively; in groups V and VI, the slices were perfused with 20 micromol/L propofol and 20 micromol/L propofol plus 5 micromol/L doxapram, respectively. The RRDA in the hypoglossal nerve was recorded by suction electrode. The discharge time course of the inspiratory (TI), expiratory (TE), respiratory cycle (RC) and integral amplitude of the inspiratory discharge (IA) were recorded at 1, 3, 5, 10, 15, and 30 min after the application of the drugs.

RESULTSThe hypoglossal nerve in groups I, II and VI showed no significant changes of RRDA in the entire course of the experiment (P>0.05). In groups III and IV, the TI, IA increased and TE decreased significantly 5 min after doxapram application (P<0.05), and the RC was shortened only at 10 min. In group V, the TI and IA decreased and the RC and TE increased significantly after the drug application (P<0.05).

CONCLUSIONDoxapram (>5 micromol/L ) can directly stimulate the RRDA and prevent propofol-induced inhibitory effects in the brainstem slice of neonatal rats, and the effects are mediated by its actions upon the inspiratory neurons in the mNRF.