Allopregnanolone and Pregnanolone Are Reduced in the Hippocampus of Epileptic Rats, but Only Allopregnanolone Correlates with Seizure Frequency

Neuroendocrinology. 2021;111(6):536-541. doi: 10.1159/000509093. Epub 2020 Jun 3.


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 neurosteroid levels 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 seizure frequency by video electrocorticography (n = 23) and compared to age-matched controls monitored in the same manner (n = 11).

Results: Decreased allopregnanolone (-50%; p < 0.05, Mann-Whitney test) and pregnanolone levels (-64%; p < 0.01) were 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 seizure frequency (r2 = 0.4606, p < 0.01).

Conclusion: 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.

Keywords: Allopregnanolone; Hippocampus; Kainic acid; LC-MS/MS; Pregnanolone; Temporal lobe epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Electrocorticography
  • Epilepsy* / metabolism
  • Epilepsy* / physiopathology
  • Hippocampus* / metabolism
  • Hippocampus* / physiopathology
  • Male
  • Neocortex / metabolism
  • Neocortex / physiopathology
  • Pregnanolone / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Status Epilepticus* / metabolism
  • Status Epilepticus* / physiopathology


  • Pregnanolone