Allopregnanolone and pregnanolone are reduced in the hippocampus of epileptic rats, but only allopregnanolone correlates with the seizure frequency

Background: Neurosteroids modulate epileptic activity by interacting with the γ-aminobutyric acid type A receptor, but their brain levels are still undetermined. Objectives: We aimed to establish levels of neurosteroids in the neocortex and hippocampus by liquid chromatography–mass spectrometry in epileptic rats. Methods: Kainic acid-treated rats were continuously monitored up to 9 weeks to determine the seizure frequency by video electrocorticography (n=23), and compared to age-matched controls monitored in the same manner (n=11). Results: A reduction in allopregnanolone (-50%; p<0.05, Mann-Whitney test) and pregnanolone levels (-64%; p<0.01) was found in the hippocampus, whereas pregnenolone sulfate, pregnenolone, progesterone, and 5α-dihydroprogesterone were nonsignificantly reduced. No changes were found in the neocortex. Moreover, allopregnanolone (but not pregnanolone) levels were positively correlated with the seizure frequency (r2=0.4606, p<0.01). Conclusions: These findings indicate a selective reduction in hippocampal levels of 3α-reduced neurosteroids. This reduction was partially mitigated by seizures in the case of allopregnanolone.