EPIPREGNANOLONE ACTS AS A PARTIAL AGONIST ON A COMMON NEUROSTEROID MODULATORY SITE OF THE GABA(A) RECEPTOR COMPLEX IN AVIAN CNS

Neurosteroid modulatory sites present in the GABA(A) receptor complex in chick optic lobe were investigated, in order to evaluate whether al lopregnanolone and alphaxalone act through a common site of action. Re sults showed that either allopregnanolone or alphaxalone present a sin gle-component enhancement of [H-3]flunitrazepam binding with EC(50) of 1.18 +/- 0.12 and 6.56 +/- 0.86 mu M and E(max) of 82.18 +/- 5.80 and 62.98 +/- 3.73 %, respectively. Epipregnanolone behaved as a partial agonist of these steroid modulatory sites with EC(50) of 0.49 +/- 0.15 mu M and E(max) 12.34 +/- 1.03 %. Moreover, the addition of 16 mu M e pipregnanolone to either allopregnanolone or alphaxalone decreased EC( 50) values to 0.54 +/- 0.09 and 1.24 +/- 0.25 mu M respectively, while E(max) values were not significantly affected. On the other hand, add itivity experiments disclosed that a maximal concentration (16 mu M) o f alphaxalone in the presence of allopregnanolone failed to enhance [H -3]flunitrazepam binding in excess of that produced by allopregnanolon e alone. Results indicate that not only allopregnanolone and alphaxalo ne act through a common site of action, but such site is highly stereo specific with regard to the neurosteroid spatial configuration.