Electrophysiological effects of allopregnanolone in rats with a history of ethanol exposure.
BACKGROUND
Sensitivity to the anticonvulsant effects of allopregnanolone (ALLO) is enhanced during the early phase of ethanol (EtOH) withdrawal. However, it is unclear whether this enhanced sensitivity generalizes to ALLO's neurobehavioral effects during protracted abstinence. The purpose of this study was to examine the neurophysiological effects of ALLO in rats with a history of chronic EtOH exposure after a protracted period of abstinence.


METHODS
Male Wistar rats were exposed to EtOH vapor for 14 hr/day for 5 weeks. Blood EtOH levels were maintained between 200 and 250 mg/dl. The effects of ALLO (0.0-10 mg/kg, intraperitoneally) on motor activity, the electroencephalogram (EEG), and auditory event-related potentials then were assessed after 6 to 8 weeks of abstinence from EtOH.


RESULTS
ALLO's effects on the EEG were consistent with previous studies and were unaffected by EtOH exposure. ALLO increased high-frequency EEG power and shifted peak EEG frequencies in a benzodiazepine- and barbiturate-like manner in both the cortex and the hippocampus. The effects of ALLO on event-related potentials were attenuated in rats with a history of EtOH exposure. Low doses of ALLO (1 and 5 mg/kg) reduced cortical P1 amplitude in response to the standard tone but only in the control group. ALLO also increased N1 amplitude in the hippocampus of the control group while having no significant effect in EtOH-exposed rats. Low doses of ALLO (1 and 5 mg/kg) were found to increase motor activity.


CONCLUSIONS
These data indicate that a history of EtOH exposure attenuates some of the neurophysiological effects of ALLO in a manner consistent with cross-tolerance. Taken together, these data suggest that increased sensitivity to ALLO's neurobehavioral effects is limited to the early phases of EtOH withdrawal and may not extend to more protracted periods of abstinence.
Slawecki
Craig J
CJ
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA. cslawecki@scripps.edu
Purdy
Robert H
RH
Ehlers
Cindy L
CL
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects*; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011280:Pregnanolone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000431:Ethanol; D011280:Pregnanolone