Interaction between 17 beta-oestradiol and 3 alpha-hydroxy-5 alpha-pregnane-20-one in the control of neuronal excitability in slices from the CA1 hippocampus in vitro of guinea-pigs and rats.

The effect of 17 beta-oestradiol and 3 alpha-hydroxy-5 alpha-pregnane-20-one (allopregnanolone) on the action potentials in the Schaffer collateral pathway was investigated in hippocampus CA1. Slices from male and female guinea-pigs and female rats were used. In the rat three groups were studied: (a) untreated prepubertal rats at day 25 after partus; (b) rats injected on day 26 with 10 IU of equine serum gonadotropin studied on day 28, when in the pro-oestrus follicular phase; and (c) on day 32 when in the luteal phase. The allopregnanolone (12.6 microM, 0.5 nL) was applied locally in stratum orienspyramidale. the 17 beta-oestradiol (0.7 nM) was perfused (4 mL min-1) or applied locally. The amplitude of the population spike in stratum pyramidale was increased by oestradiol in guinea-pigs of both sexes and in all the three groups of rats. Allopregnanolone decreased the amplitude of the population spike in the guinea-pigs and in the luteal phase rats. The effect appeared within seconds after the application of the drugs. The allopregnanolone inhibition of the population spike was increased by perfusion with oestradiol in the guinea-pigs and in the luteal phase rats. This effect appeared within 7 min, and improved with increasing length of the perfusion (7-71 min). It remained for 55 min after return to perfusion with artificial cerebrospinal fluid. In prepubertal and follicular phase rats the allopregnanolone inhibition was seen only after perfusion with oestradiol for more than 15 min. The results show that 17 beta-oestradiol increases the allopregnanolone inhibition and that this inhibition is most efficient during the luteal phase of the rat.