Interaction between 3 alpha-hydroxy-5 alpha-pregnan-20-one and carbachol in the control of neuronal excitability in hippocampal slices of female rats in defined phases of the oestrus.

The effects of 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) and carbachol on CA1 and dentate gyrus action potentials were studied in hippocampus slices in premature, follicular and luteal phase rats. A 0.5 nL droplet of allopregnanolone (12.5 mumol L-1), carbachol (5 mumol L-1) or a mixed solution of 12.5 mumol L-1 allopregnanolone and 5 mumol L-1 carbachol was applied locally onto the stratum oriens-pyramidale or granular layer. The amplitude of CA1 population spike (POPSP) was reduced by allopregnanolone (-38 +/- 3%) and carbachol (-21 +/- 4%) in the luteal phase slices. The mixture of allopregnanolone and carbachol doubled this inhibition (-77 +/- 6%). The inhibition caused by allopregnanolone and the mixture of allopregnanolone and carbachol in CA1 was significantly larger in the luteal phase than in the follicular phase (P = 0.02 and 0.0002). In the granular layer of the dentate gyrus, these inhibitions showed no significant difference between the phases. Neither in CA1 nor in the dentate gyrus did the carbachol inhibition differ between the phases. Perfusion with 5-10 mumol L-1 carbachol caused an increasing inhibition of the POPSP during the first few minutes. Thereafter the inhibition gradually diminished and was replaced by a facilitation. The local allopregnanolone inhibition was enhanced by simultaneous carbachol perfusion. Picrotoxin (100 mumol L-1) substantially reduced the allopregnanolone but not the carbachol inhibition. Atropine (10 mumol L-1) blocked the carbachol response, but not the allopregnanolone inhibition. Perfusion with a mixed solution of picrotoxin and atropine reduced, but did not block, the inhibition caused by local application of allopregnanolone or by the mixture of allopregnanolone and carbachol. Our data suggest that neuroprogestine modulators of the GABAA-receptor-mediated inhibition may play a significant role in the control of the cholinergic excitation in the hippocampus.