PRESYNAPTIC ACTION OF THE NEUROSTEROID PREGNENOLONE SULFATE ON INHIBITORY TRANSMITTER RELEASE IN CULTURED HIPPOCAMPAL-NEURONS

The effects of the neurosteroid pregnenolone sulfate (PS) were studied in 3- to 9-week-old hippocampal cultures from neonatal rats. Cells we re voltage clamped using CsCl filled electrodes, while action potentia ls and excitatory glutamatergic currents were abolished by superfusing with a combination of tetrodotoxin, 6-cyano-7-nitroquinoxaline (CNQX) and 2-amino-5-phosphonopentanoic acid (AP-5), Under these conditions spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) were s een as inward currents at a holding potential of -70 mV. Their amplitu de distributions were skewed without clearly detectable peaks. PS at 1 -50 mu M concentrations decreased the frequency of sIPSCs, with 1 mu M being the most effective concentration. The effect appeared after 10- 15 min of steroid application and the magnitude of the reduction incre ased during the early wash period. No recovery of sIPSC frequency was found after 30 min of washing with steroid-free medium. sIPSC amplitud es were not significantly changed at the time the effect of PS on sIPS C frequency was observed. The slow onset of this effect and its durati on suggest a novel presynaptic action of the neurosteroid PS on GABAer gic inhibition in the mammalian brain. (C) 1997 Elsevier Science B.V.