Comparison of the neurophysiological effects of allopregnanolone and ethanol in rats

Rationale: The central nervous system actions of allopregnanolone (3 alpha- hydroxy-5 alpha-pregnan-20-one) and ethanol are at least partially mediated by modulation of gamma-aminobutyric acid (GABA)-A receptors. Although etha nol and allopregnanolone have similar behavioral effects, their macro-elect rophysiological profiles have not been directly compared. Objective: The pu rpose of this study was to compare the effects of allopregnanolone and etha nol on the electroencephalogram (EEG) and event-related potentials (ERPs). Methods: Male Wistar rats were implanted with cortical and amygdalar electr odes. The rats were then administered allopregnanolone (0.0-10 mg/kg), etha nol (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 amplit ude in the amygdala by 75-80%. Combined administration of ethanol (0.50 g/k g) and allopregnanolone (5.0 mg/kg), doses which were ineffective alone, de creased N1 amplitude in the amygdala by 60%. Allopregnanolone and ethanol h ad dissimilar EEC effects. Allopregnanolone increased high frequency power in the cortex and amygdala by 35-30%. Ethanol decreased cortical and amygda lar power in the same high frequency bands by 25-45%. Allopregnanolone, but not ethanol, also shifted cortical frequency in the 32- to 50-Hz band. Com bined administration of allopregnanolone and ethanol had no effect on EEG p ower but enhanced allopregnanolone's effect on cortical frequency. Conclusi ons: These data suggest that allopregnanolone's macro-electrophysiological profile resembles barbiturates and benzodiazepines more than ethanol. Furth er, the interactions of allopregnanolone and ethanol appear complex, with m ultiple effects observed (enhancement or reversal) depending on the neuroph ysiological variable assessed.