The neurosteroid pregnenolone sulphate enhances NMDA-induced phasic firing of vasopressin neurones in the rat supraoptic nucleus.

The effect of the neurosteroid pregnenolone sulphate (PS) on N-methyl-D-aspartate (NMDA)-induced phasic firing of supraoptic vasopressin (VP) neurones was studied in rat hypothalamic slices in vitro. In VP neurones which were induced to fire phasically by continuous perifusion with NMDA (9-30 microM), addition of 100 microM PS to the incubation medium significantly increased overall spike frequency, with a rise in both proportion of time active and intraburst firing rate. A similar effect was seen during picrotoxin block of GABAergic transmission. No significant change in NMDA-induced phasic firing was observed with 100 microM dehydroepiandrosterone sulphate. VP neurones became silent in the absence of NMDA, and under these conditions PS had no effect. In conclusion, PS increases NMDA-induced phasic firing in VP neurones, providing a mechanism whereby this neurosteroid may participate in the regulation of VP secretion.