期刊
BIOLOGICAL PSYCHIATRY
卷 61, 期 1, 页码 78-86出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2006.03.063
关键词
alcohol; dependence; withdrawal; corticotropin-releasing factor; self-administration; rat
资金
- Intramural NIH HHS Funding Source: Medline
- NIAAA NIH HHS [AA12602, AA015239, R01 AA012602-08, F32 AA015239, R01 AA012602] Funding Source: Medline
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [Z01DK059501] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R01AA012602, F32AA015239] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [Z01DA000520] Funding Source: NIH RePORTER
Background: Alcohol dependence is characterized by excessive alcohol consumption, loss of control over intake, and the presence of a withdrawal syndrome, which includes both motivational and physical symptoms. Similar to human alcoholics, ethanol-dependent animals display enhanced anxiety-like behaviors and enhanced ethanol self-administration during withdrawal, (effects hypothesized to result from a dysregulation of corticotropin-releasing factor (CRF) stress systems. Here, we used an animal model of ethanol dependence to test the effects of CRF1 receptor antagonists on excessive ethanol self-administration in dependent rats. Methods. Wistar rats, trained to orally self-administer ethanol, were exposed intermittently to ethanol vapors to induce ethanol dependence. Nondependent animals were. exposed to control air. Following a 2-hour period of withdrawal, dependent and nondependent animals were systemically administered antalarmin, MJL-1-109-2, or R121919 (CRF, antagonists) and ethanol self-administration was measured. Results: The nonpeptide, small molecule CRF1 antagonists selectively reduced excessive self-administration of ethanol in dependent animals during acute withdrawal. The antagonists bad no effect on ethanol self-administration in nondependent rats. Conclusions: These data demonstrate that CRF1 receptors play an important role in mediating excessive ethanol self-administration in dependent rats, with no effect in nondependent rats. CRF1 antagonists may be exciting new pharmacotherapeutic targets for the treatment of alcoholism in humans.
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