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 ESTRUS

The effects of 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolon e) and carbachol on CA1 and dentate gyrus action potentials were studi ed in hippocampus slices in premature, follicular and luteal phase rat s. A 0.5 nL droplet of allopregnanolone (12.5 mu mol L-1), carbachol ( 5 mu mol L-1) or a mixed solution of 12.5 mu mol L-1 allopregnanolone and 5 mu mol 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 a nd carbachol doubled this inhibition (-77 +/- 6%). The inhibition caus ed by allopregnanolone and the mixture of allopregnanolone and carbach ol in CA1 was significantly larger in the luteal phase than in the fol licular phase (P = 0.02 and 0.0002). In the granular layer of the dent ate 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 mu mol L-1 c arbachol caused an increasing inhibition of the POPSP during the first few minutes. Thereafter the inhibition gradually diminished and was r eplaced by a facilitation. The local allopregnanolone inhibition was e nhanced by simultaneous carbachol perfusion. Picrotoxin (100 mu mol L- 1) substantially reduced the allopregnanolone but not the carbachol in hibition. Atropine (10 mu mol 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 a llopregnanolone and carbachol, Our data suggest that neuroprogestine m odulators of the GABAA-receptor-mediated inhibition may play a signifi cant role in the control of the cholinergic excitation in the hippocam pus.