The opioid peptides enkephalin and beta-endorphin in alcohol dependence.
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.
Racz
Ildiko
I
Institute of Molecular Psychiatry, Life & Brain Center, University of Bonn, Bonn, Germany. iracz@uni-bonn.de
Schürmann
Britta
B
Karpushova
Anna
A
Reuter
Martin
M
Cichon
Sven
S
Montag
Christian
C
Fürst
Robert
R
Schütz
Christian
C
Franke
Petra E
PE
Strohmaier
Jana
J
Wienker
Thomas F
TF
Terenius
Lars
L
Osby
Urban
U
Gunnar
Agneta
A
Maier
Wolfgang
W
Bilkei-Gorzó
Andras
A
Nöthen
Markus
M
Zimmer
Andreas
A
D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology*; D000437:Alcoholism / Q000209:etiology / Q000235:genetics*; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D002755:Choice Behavior / Q000502:physiology; D004195:Disease Models, Animal; D004745:Enkephalins / Q000172:deficiency / Q000235:genetics*; D005260:Female; D005518:Food Preferences / Q000502:physiology; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000150:complications; D001615:beta-Endorphin / Q000172:deficiency / Q000235:genetics*
D004745:Enkephalins; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin