Comparison of the neurophysiological effects of allopregnanolone and ethanol in rats

Abstract 

Rationale: The central nervous system actions of allopregnanolone (3α-hydroxy-5α-pregnan-20-one) and ethanol are at least partially mediated by modulation of γ-aminobutyric acid (GABA)-A receptors. Although ethanol and allopregnanolone have similar behavioral effects, their macro-electrophysiological profiles have not been directly compared. Objective: The purpose of this study was to compare the effects of allopregnanolone and ethanol on the electroencephalogram (EEG) and event-related potentials (ERPs). Methods: Male Wistar rats were implanted with cortical and amygdalar electrodes. The rats were then administered allopregnanolone (0.0–10 mg/kg), ethanol (0.0–1.0 g/kg), or a combination of the two before recording. Results: Allopregnanolone and ethanol had similar effects on ERPs. When administered alone, both decreased cortical P1-N1 ERP amplitude by 25–50% and N1 amplitude in the amygdala by 75–80%. Combined administration of ethanol (0.50 g/kg) and allopregnanolone (5.0 mg/kg), doses which were ineffective alone, decreased N1 amplitude in the amygdala by 60%. Allopregnanolone and ethanol had dissimilar EEG effects. Allopregnanolone increased high frequency power in the cortex and amygdala by 25–30%. Ethanol decreased cortical and amygdalar power in the same high frequency bands by 25–45%. Allo- pregnanolone, but not ethanol, also shifted cortical frequency in the 32- to 50-Hz band. Combined administration of allopregnanolone and ethanol had no effect on EEG power but enhanced allopregnanolone’s effect on cortical frequency. Conclusions: These data suggest that allopregnanolone’s macro-electrophysiological profile resembles barbiturates and benzodiazepines more than ethanol. Further, the interactions of allopregnanolone and ethanol appear complex, with multiple effects observed (enhancement or reversal) depending on the neurophysiological variable assessed.