Properties of whole-cell glycine currents (I-Gly) of ventral tegmental area (VTA) neurons from 3- to 7-day old Sprague-Dawley rats were investigated with the patch-clamp technique. Ninety-three percent of the 126 neurons examined produced I-Gly in response to glycine. For 70% of these neurons, I-Gly did not decay in response to a threshold concentration of glycine (1-5 mu M). At elevated glycine concentrations, I-Gly consistently decayed from a peak to a steady state (SS). I-Gly increased in amplitude sigmoidally as a function of the concentration of agonist with an EC50 of 32 mu M. Strychnine (STR), when co-applied with glycine after a prepulse of STR, suppressed both the peak and SS I-Gly noncompetitively. In the absence of a prepulse, STR had a smaller effect on peak I-Gly while increasing its decay rate; the SS amplitude decreased. These STR effects were concentration dependent with an IC50 of 31 nM and 184 nM STR for the peak and SS I-Gly, with prepulse, respectively, and 732 nM and 193 nM for the peak and SS I-Gly, respectively, without prepulse. Picrotoxin (PTX) co-applied with glycine suppressed both the peak and the SS I-Gly with an IC50 of 25 mu M. In contrast to STR, 1 min preincubation with PTX had no effect on I-Gly. Thus, PTX acts on the open channel. The inhibitory effects of both STR and PTX on I-Gly did not depend on the membrane potential. (C) 1998 Elsevier Science B.V. All rights reserved.