MODULATION OF THE GABA(A) 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 ventromedi al hypothalamic neurons were investigated using the nystatin perforate d patch recording mode under voltage-clamp conditions. The PGN at conc entrations between 10(-7) and 10(-5) M evoked an inward current at a h olding potential (VH) of -40 mV. The reversal potential of the PGN-ind uced current was close to the equilibrium potential of Cl-. PGN potent iated the GABA-induced Cl- current in a concentration dependent manner . The facilitatory effect was long lasting and disappeared slowly afte r being washed out. The effect of PGN on the GABA response was also af fected by the pretreatment time of PGN. PGN shifted the concentration- response relationship for GABA to the left with a suppression of the m aximal response to GABA, resulting from the rapid inactivation of the GABA response during PGN treatment. Facilitatory interactions were fou nd to exist among GABA, pentobarbital, diazepam, and PGN. Three other PGN isomers were also effective in facilitating the GABA response. How ever, the isomers containing the 3 alpha-hydroxy configurations potent iated the GABA response much more potently and only these isomers exhi bited inward Currents themselves. (C) 1997 Elsevier Science Inc.