Amino-acid induced depression of cortical neurones

1. The effects of strychnine on the degree of depression of neuronal firing induced by glycine, gamma-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT) have been examined quantitatively. All drugs were applied by iontophoresis to spontaneously active cerebral cortical neurones in the anaesthetized cat. The application of these drugs was continued until a plateau or equilibrium depression was reached. The time taken to reach this steady state was noted. Dose-response curves were then constructed for those currents giving less than complete depression.2. Glycine was less potent than GABA and about 7-fold larger currents were needed to achieve comparable depression. 5-HT was also a weak depressant compared with GABA and had 0.6 the potency of glycine on a current basis.3. Strychnine in currents up to 25 nA shifted the dose-response curve of glycine to the right at a time when equilibrium depression in the same cells induced by the control agonists GABA or 5-HT was unaffected. These currents of strychnine did, however, prolong the time-course of onset of GABA and 5-HT depression.4. In larger currents strychnine reduced GABA equilibrium depression, but the dose-response curve was not shifted in a parallel fashion.5. It is concluded that strychnine can specifically and competitively antagonize the effect of glycine on cortical neurones.