Modulation of the GABAA-like autoreceptor by barbiturates but not by steroids

In slices of cerebral cortex from rat preloaded with [3H]GABA, muscimol produced a concentration-related inhibition of K(+)-evoked release of tritium with a pIC25 value of 7.80 +/- 0.39. Dimethylbarbituric acid (10 and 100 microM) and pentobarbitone (100 microM) significantly increased this value to 8.31 +/- 0.09, 9.91 +/- 0.21 and 8.50 +/- 0.21, respectively, whereas the steroid ligands alphaxalone (1 microM) and 5 beta-pregnane-3 alpha-ol-20-one (10 nM) had no significant effect. The 5 beta-pregnane-3 alpha-ol-20-one and 5 beta-pregnane-3,20-dione produced a concentration-related increase in K(+)-evoked release of tritium alone. These data suggest that the GABAA-like autoreceptor may be modulated by barbiturates but not by steroids and thus may be different from the postsynaptic GABAA receptor.