INHIBITION OF GLYCINE CURRENTS BY DEXTROMETHORPHAN IN NEURONS DISSOCIATED FROM THE GUINEA-PIG NUCLEUS-TRACTUS-SOLITARII

1. The effect of dextromethorphan (DM) on the current induced by glyci ne in acutely dissociated nucleus tractus solitarii (NTS) neurones of guinea-pigs was studied by use of the whole-cell patch clamp technique . The effect of DM on gamma-aminobutyric acid (GABA)-induced currents (I-GABA) was also examined. 2 DM inhibited 30 mu M glycine-induced cur rent (I-Gly), without affecting the current caused by 30 mu M GABA. Th e action of DM was concentration-dependent, with a maximum effect at 1 00 mu M, and reversible. The half-maximum inhibitory concentration (IC 50) of DM was 3.3 mu M, about 85 times higher than that of strychnine. 3 DIM 3 mu M shifted the concentration-response curve for glycine to the right without affecting the maximum value. DM 10 mu M shifted the curve even more to the right, although it was not a parallel shift. St rychnine at a concentration of 0.1 mu M shifted the curve for glycine in a nearly parallel fashion. 4 The effect of 10 mu M DM was slightly weak voltage-dependency, but the lower concentration of DM, 3 mu M, in hibited I-Gly equally at -50 mV and +50 mV. The effect of 3 mu M DM on I-Gly showed no use-dependence. Blockade by strychnine 0.1 mu M showe d no voltage- or use-dependence. 5 The results indicate that DM inhibi ts I-Gly in single neurones of NTS, and further suggest that DM at a l ow concentration may act on the glycine receptor-ionophore complex, bu t not on the Cl- channel of the complex. However, a relatively high co ncentration of DM may at least partly affect the Cl- channel of the co mplex.