A method for comparing the potencies of -aminobutyric acid antagonists on single cortical neurones using micro-iontophoretic techniques.

1. By the use of micro-iontophoretic techniques, quantitative estimates of the depressant effect of gamma-aminobutyric acid (GABA) have been obtained from single neurones in the middle suprasylvian gyrus of cat cerebral cortex.2. The progressive reduction in firing rate of the neurone during each microiontophoretic application of GABA was followed until inhibition was complete. The resultant time-response curves represented cumulative concentration-response relationships which could be characterized by measuring the time taken to achieve 50% inhibition (T50) of neuronal firing.3. The time-response curves for GABA could be displaced along the time axis by micro-iontophoretic application of picrotoxin, bicuculline or strychnine. A displaced curve was more nearly parallel to the control curve when responses were plotted against linear rather than log time.4. Picrotoxin usually increased T50 values for GABA, bicuculline could both increase and decrease them and strychnine usually decreased them.5. When displacements of GABA response curves were expressed as difference between T50 (test-control)/T50 (control), the values obtained were minimally influenced by the size of the current applying GABA and were unaffected by changes in the retaining current passed through the GABA barrel between applications.6. The use of this method to compare the micro-iontophoretic potencies of different GABA antagonists is discussed.