This study was supported by AA08459 from the National Institute on Alcohol Abuse and Alcoholism (GFK). GRV was supported by Individual National Research Service Award AA05563 from the National Institute on Alcohol Abuse and Alcoholism. EPZ was supported by a Minority Research Supplement to DK26741 from the National Institute of Diabetes and Digestive and Kidney Diseases.
Increased Ethanol Self-Administration and Anxiety-Like Behavior During Acute Ethanol Withdrawal and Protracted Abstinence: Regulation by Corticotropin-Releasing Factor
Article first published online: 11 APR 2006
Alcoholism: Clinical and Experimental Research
Volume 26, Issue 10, pages 1494–1501, October 2002
How to Cite
Valdez, G. R., Roberts, A. J., Chan, K., Davis, H., Brennan, M., Zorrilla, E. P. and Koob, G. F. (2002), Increased Ethanol Self-Administration and Anxiety-Like Behavior During Acute Ethanol Withdrawal and Protracted Abstinence: Regulation by Corticotropin-Releasing Factor. Alcoholism: Clinical and Experimental Research, 26: 1494–1501. doi: 10.1111/j.1530-0277.2002.tb02448.x
- Issue published online: 11 APR 2006
- Article first published online: 11 APR 2006
- Received for publication November 5, 2001; accepted July 17, 2002.
- Protracted Abstinence;
Background Animal models of alcohol dependence suggest that long-term alterations in brain corticotropin-releasing factor (CRF) systems, key mediators of the behavioral stress response, may be involved in the development and reinstatement of dependence on drugs of abuse. The objective of the present study was to investigate the role of CRF in the regulation of ethanol self-administration and to examine the behavioral stress response during acute withdrawal and protracted abstinence.
Methods Male Wistar rats were made dependent on ethanol via chronic exposure to ethanol vapor. Ethanol self-administration and exploratory behavior in the elevated plus maze were measured at 2 hr and 3 to 5 weeks after exposure. The role of CRF in ethanol self-administration was examined via central injection of the CRF receptor antagonist D-Phe-CRF(12–41).
Results Rats showed increased responding for ethanol 2 hr and 3 to 5 weeks after chronic ethanol exposure, which was attenuated by central injection of D-Phe-CRF(12–41). In addition, rats displayed a decrease in open-arm exploration in the elevated plus maze when tested 2 hr and 4 weeks after exposure.
Conclusions These results indicate that chronic ethanol exposure leads to increased ethanol self-administration and decreased open-arm exploration in the elevated plus maze during acute withdrawal and protracted abstinence. Attenuation of ethanol self-administration via central injection of D-Phe-CRF(12–41) implicates CRF as an underlying mechanism regulating long-term motivational effects associated with alcohol dependence.