The opioid peptides enkephalin and beta-endorphin in alcohol dependence.

Abstract

BACKGROUND:

Experimental evidence indicates that the endogenous opioid system influences stress responses as well as reinforces effects of addictive drugs. Because stress is an important factor contributing to drug dependence and relapse, we have now studied ethanol preference in enkephalin- and beta-endorphin-deficient mice under baseline conditions and after stress exposure.

METHODS:

In the present study we used a two-bottle choice paradigm to study ethanol consumption and stress-induced ethanol preference. To examine alcohol withdrawal symptoms the forced drinking procedure was employed. We performed an association analysis in two case-control samples of alcohol addicts to determine whether these opioid peptides also contribute to ethanol dependence in humans.

RESULTS:

Ethanol consumption was significantly reduced in the absence of beta-endorphins, particularly in female knockout animals. Stress exposure results in an increased ethanol consumption in wild-type mice but did not influence ethanol-drinking in beta-endorphin knockouts. Enkephalin-deficient mice showed no difference from wild-type mice in baseline ethanol preference but also showed no stress-induced elevation of ethanol consumption. Interestingly, we found a two-marker haplotype in the POMC gene that was associated with alcohol dependence in females in both cohorts.

CONCLUSIONS:

Together these results indicate a contribution of beta-endorphin to ethanol consumption and dependence.

• Authors: Ildiko Racz, Britta Schürmann, Anna Karpushova, Martin Reuter, Sven Cichon, Christian Montag, Robert Fürst, Christian Schütz, Petra E Franke, Jana Strohmaier, Thomas F Wienker, Lars Terenius, Urban Osby, Agneta Gunnar, Wolfgang Maier, Andras Bilkei-Gorzó, Markus Nöthen, Andreas Zimmer
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 64 Issue 11 Pg. 989-97 (Dec 01 2008) ISSN: 1873-2402 [Electronic] United States
• PMID: 18589403 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Enkephalins
• beta-Endorphin
• Pro-Opiomelanocortin

Topics

• Adult
• Alcohol Drinking (genetics, physiopathology, psychology)
• Alcoholism (etiology, genetics)
• Animals
• Body Weight (drug effects, genetics)
• Choice Behavior (physiology)
• Disease Models, Animal
• Enkephalins (deficiency, genetics)
• Female
• Food Preferences (physiology)
• Gene Frequency
• Genotype
• Humans
• Linkage Disequilibrium
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Pro-Opiomelanocortin (genetics)
• Sex Characteristics
• Stress, Psychological (complications)
• beta-Endorphin (deficiency, genetics)