OBJECTIVETo investigate the role of GABA A receptor in nikethamide-induced respiratory enhancement in the medullary slices of neonatal rats.

METHODSEx vivo medullary slices of neonatal rats (1 to 3 days old) containing the medial region of the nucleus retrofacialis with the hypoglossal nerve rootlets were prepared and perfused with modified Kreb's solution to record respiration-related rhythmic discharge activity (RRDA) from the hypoglossal nerve rootlets using suction electrodes. Thirty RRDA-positive slices were randomized into 5 equal groups and perfused with nikethamide (at concentrations of 0.5, 1, 3, 5, 7, and 10 microg/ml with the optimal nikethamide concentration determined), GABA (at 10, 20, 40, and 60 micromol/ to determine the optimal concentration), 10 micromol/ bicuculline, 10 micromol/ bicuculline plus 40 micromol/L GABA, and 5 microg/ml nikethamide followed by 5 microg/ml nikethamide plus 10 micromol/ bicuculline after wash out, respectively.

RESULTSNikethamide increased RRDA at the concentrations of 0.5-7 microg/ml, and 5 microg/ml nikethamide showed the most distinct effect on the inspiratory time (TI), integral amplitude (IA), and respiratory cycle (RC). GABA at 40 micromol/ showed the most effective inhibition of RRDA in terms of TI, IA, and RC. Bicuculline at 10 micromol/ could increase the IA, TI and RC, but the combination of 10 micromol/ bicuculline and 40 micromol/ GABA had no significant effects on RRDA. Compared with nikethamide used alone, nikethamide plus bicuculline significantly increased TI and IA without affecting RC.

CONCLUSIONNikethamide can enhance RRDA of the hypoglossal nerve rootlets in the medullary slices of neonatal rats, and the effect can be partially mediated by the GABA A receptor.