Modulation of the GABAA response in rat ventromedial hypothalamic neurons by pregnanolone

The effects of 5 beta,3 alpha-pregnanolone (PGN) on gamma-aminobutyric acid (GABA)-induced Cl- current in acutely dissociated rat ventromedial hypothalamic neurons were investigated using the nystatin perforated patch recording mode under voltage-clamp conditions. The PGN at concentrations between 10(-7) and 10(-5) M evoked an inward current at a holding potential (VH) of -40 mV. The reversal potential of the PGN-induced current was close to the equilibrium potential of Cl-. PGN potentiated the GABA-induced Cl- current in a concentration-dependent manner. The facilitatory effect was long lasting and disappeared slowly after being washed out. The effect of PGN on the GABA response was also affected by the pretreatment time of PGN. PGN shifted the concentration-response relationship for GABA to the left with a suppression of the maximal response to GABA, resulting from the rapid inactivation of the GABA response during PGN treatment. Facilitatory interactions were found to exist among GABA, pentobarbital, diazepam, and PGN. Three other PGN isomers were also effective in facilitating the GABA response. However, the isomers containing the 3 alpha-hydroxy configurations potentiated the GABA response much more potently and only these isomers exhibited inward currents themselves.