Inhibition by the neurosteroid allopregnanolone of basal and stress-induced acetylcholine release in the brain of freely moving rats.

The neurosteroid allopregnanolone is a potent and efficacious modulator of gamma-aminobutyric acid (GABA) type A receptors. The effects of intracerebroventricular injection of allopregnanolone (5 to 15 micrograms/5 microliters) on basal and stress-induced release of acetylcholine were investigated in various regions of the brain areas of freely moving rats and compared with those of the benzodiazepine midazolam (1 to 10 micrograms/5 microliters). Allopregnanolone inhibited (20-55%) basal acetylcholine release from the prefrontal cortex and hippocampus, but not from the striatum, in a dose-dependent manner. At a dose of 10 micrograms, allopregnanolone also completely prevented the increase in hippocampal acetylcholine release induced by foot-shock stress. Midazolam, inhibited basal acetylcholine release in all three brain regions as well as stress-induced acetylcholine release in the hippocampus, and showed a greater potency in these effects than allopregnanolone. These results suggest that endogenous neurosteroids may participate in the GABAergic modulation of central cholinergic function during basal conditions as well as after stress.