Pregnenolone and pregnenolone sulfate, alone and with ethanol, in mice on the plus-maze

The neurosteroids pregnenolone and pregnenolone sulfate were tested for anxiogenic/anxiolytic effects in mice on the elevated plus-maze. Pregnenolone in a dose of 0.01 micrograms/kg increased motor activity and caused an anxiogenic response, i.e., a decreased number of entries onto the open arms of the plus-maze. Pregnenolone sulfate had no effect on motor activity in the doses tested but showed a biphasic response on the plus-maze: at 10.0 and 1.0 micrograms/kg pregnenolone sulfate caused an anxiogenic response but at 0.1 microgram/kg it produced an anxiolytic response. When administered with 1.5 g/kg ethanol, neither neurosteroid altered the depression in motor activity caused by ethanol. However, all doses of pregnenolone tested blocked the anxiolytic effect of ethanol on the plus-maze while one dose of pregnenolone sulfate, 1.0 microgram/kg, attenuated the response to ethanol. These results support the suggestion that these neurosteroids could play a role in the initial response to stress and indicate that further work needs to be done to determine the mechanism for the interaction with ethanol.