Development of acute tolerance during steady-state arterial alcohol concentrations: a study of auditory event-related potentials in rats.
BACKGROUND
The blood alcohol clamp is a method whereby alcohol is infused intravenously to maintain a predetermined arterial alcohol concentration (AAC) for an indefinite period of time. The objective of this study was to use the clamp to examine the effects of alcohol on event-related potentials (ERPs) in rats and to assess the development of tolerance during a single alcohol exposure.


METHODS
Adult male Wistar rats that had a chronic implant of EEG electrodes overlying the frontal cortex and were equipped with cannulae in the jugular vein, were clamped at 75 or 150 mg/dl via an intravenous infusion of 20% (v/v) alcohol. Auditory ERPs were recorded before the alcohol infusion (baseline) and at 5, 15, 120, 135, or 195 min after steady-state AAC was achieved. In a separate group of rats, test-retest reliability was examined by acquiring ERPs two to three times in the same rat at 60-min intervals. Dependent variables were calculated as changes from baseline for each time point for P1-N1 amplitude and P1 and N1 latencies.


RESULTS
In the test-retest study, there were no differences in any of the dependent variables over time, indicating that the measures were stable and repeatable. Estimated AACs of 75 and 150 mg/dl significantly (p = 0.0001) decreased P1-N1 amplitude in a dose-related manner. During both clamps, the alcohol effect peaked at 120 min (p < 0.03) and decreased thereafter. Alcohol had no effect on P1 or N1 latencies.


CONCLUSIONS
Pharmacologically relevant AACs significantly decreased the amplitude but not the latencies of the long-latency components of the rat auditory ERP. Acute tolerance developed because the amplitude of the ERP component recovered as AACs were held relatively constant.
Morzorati
Sandra L
SL
Department of Psychiatry, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202, USA. smorzora@iupui.edu
Stewart
Robert B
RB
D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004569:Electroencephalography / Q000187:drug effects; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D005625:Frontal Lobe / Q000187:drug effects / Q000502:physiology; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results
D002492:Central Nervous System Depressants; D000431:Ethanol