The study was supported by P50 AA11605 and NRSA AA05519 grants from NIAAA. The P rats obtained from the Indiana Alcohol Research Center were supported by P50-AA07611 from NIAAA.
P Rats Develop Physical Dependence on Alcohol Via Voluntary Drinking: Changes in Seizure Thresholds, Anxiety, and Patterns of Alcohol Drinking
Article first published online: 30 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 24, Issue 3, pages 278–284, March 2000
How to Cite
Kampov-Polevoy, A. B., Matthews, D. B., Gause, L., Morrow, A. L. and Overstreet, D. H. (2000), P Rats Develop Physical Dependence on Alcohol Via Voluntary Drinking: Changes in Seizure Thresholds, Anxiety, and Patterns of Alcohol Drinking. Alcoholism: Clinical and Experimental Research, 24: 278–284. doi: 10.1111/j.1530-0277.2000.tb04608.x
- Issue published online: 30 MAY 2006
- Article first published online: 30 MAY 2006
- Received for publication September 13, 1999; accepted January 6, 2000
- P Rats;
- Alcohol withdrawal;
Background: It has been proposed that the alcohol-preferring P rat meets many of the criteria for an animal model of alcoholism. However, the development of alcohol dependence has not been explored in rats that self-administer ethanol for less than 15–20 weeks. The present study investigated the development of physical dependence upon alcohol after 2–6 weeks of voluntary alcohol intake. Changes in bicuculline-induced seizure thresholds, microstructure of alcohol drinking, and anxiety-related behavior were used as indices of alcohol dependence. In addition, we evaluated the microstructure of alcohol drinking associated with the development of physical dependence upon alcohol.
Methods: Alcohol (10% ethanol solution) was measured in graduated drinking tubes with both alcohol and water available continuously. Microstructure of alcohol intake was monitored by a computerized drinkometer. Physical dependence upon alcohol was determined by measuring bicuculline-induced seizure thresholds after alcohol withdrawal. Anxiety-related behavior of P rats after alcohol withdrawal was determined by the social interaction and elevated plus maze tests.
Results: Initial alcohol intake in the alcohol-preferring P rat was relatively modest (3.9 ± 0.4 g/kg/day). Four days of forced alcohol exposure (initiation) followed by 6 weeks of voluntary drinking resulted in an increase of alcohol intake to 5.5 ± 0.2 g/kg/day. Ethanol self-administration for 6 weeks, but not for 2 or 4 weeks, produced a significant reduction (30%; p < 0.05) in bicuculline-induced seizure thresholds during alcohol withdrawal. Alterations in the microstructure of alcohol intake (i.e., 90% increase in the size of alcohol drinking bouts compared to the baseline [p < 0.001] with no change in bout frequency) were associated with the development of alcohol dependence. Termination of alcohol intake after 6 weeks of voluntary alcohol consumption resulted in increased anxiety according to both the social interaction and elevated plus maze tests.
Conclusions: The results of this study indicate that 6 weeks of voluntary alcohol intake are sufficient for the development of physical dependence upon alcohol in the alcohol-preferring P rats as measured by susceptibility to bicuculline-induced seizures. This time is much shorter than the 15–20 weeks reported earlier. Development of physical dependence to alcohol was associated with an increase in daily alcohol intake (40% over the baseline), an increase in alcohol intake during each drinking bout (90% over the baseline), and elevated anxiety during alcohol withdrawal.