MODULATION OF THE GABA(A)-LIKE AUTORECEPTOR BY BARBITURATES BUT NOT BY STEROIDS

In slices of cerebral cortex from rat preloaded with [H-3]GABA, muscim ol 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 mu M) and pentobarbitone (I 00 mu M) significantly increas ed this value to 8.31 +/- 0.09, 9.91 +/- 0.21 and 8.50 +/- 0.21, respe ctively, whereas the steroid ligands alphaxalone (1 mu M) and 5beta-pr egnane-3alpha-ol-20-one (10 nM) had no significant effect. The 5beta-p regnane-3alpha-ol-20-one and 5beta-pregnane-3,20-dione produced a conc entration-related increase in K+-evoked release of tritium alone. Thes e data suggest that the GABA(A)-like autoreceptor may be modulated by barbiturates but not by steroids and thus may be different from the po stsynaptic GABA(A) receptor.