Comparison of the neurophysiological effects of allopregnanolone and ethanol in rats.
BACKGROUND
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 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%. Allopregnanolone, 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.
Slawecki
C J
CJ
Scripps Research Institute, Department of Neuropharmacology, La Jolla, CA 92037, USA. cslawecki@scripps.edu
Walpole
T
T
Purdy
R H
RH
Ehlers
C L
CL
D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D004569:Electroencephalography / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D011280:Pregnanolone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D000431:Ethanol; D011280:Pregnanolone