Supported by Public Health Service Grants RO1 AA10722 and AA12832 from the National Institute on Alcohol Abuse and Alcoholism.
Development of Acute Tolerance During Steady-State Arterial Alcohol Concentrations: A Study of Auditory Event-Related Potentials in Rats
Article first published online: 3 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 29, Issue 3, pages 347–352, March 2005
How to Cite
Morzorati, S. L. and Stewart, R. B. (2005), Development of Acute Tolerance During Steady-State Arterial Alcohol Concentrations: A Study of Auditory Event-Related Potentials in Rats. Alcoholism: Clinical and Experimental Research, 29: 347–352. doi: 10.1097/01.ALC.0000156124.26146.89
- Issue published online: 3 MAY 2006
- Article first published online: 3 MAY 2006
- Received for publication September 17, 2004; accepted November 16, 2004.
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.
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.
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.
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.