The Opioid Peptides Enkephalin and β-Endorphin in Alcohol Dependence

Institute of Molecular Psychiatry, Life & Brain Center, University of Bonn, Bonn, Germany.
Biological psychiatry (Impact Factor: 10.26). 07/2008; 64(11):989-97. DOI: 10.1016/j.biopsych.2008.05.008
Source: PubMed


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

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Available from: Ildiko Racz
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    • "In support, endogenous enkephalins are necessary for NAL-CPA (Skoubis et al. 2005) but not opioid-induced CPP (Marquez et al. 2006) whereas mu opioid receptors are necessary for both phenotypes (Matthes et al. 1996; Skoubis et al. 2001). Interestingly, NAL-CPA-prone J mice also drink more ethanol than C57BL/6N mice from the Charles River vendor (Bryant et al. 2008) and this behavior is in part mediated by endogenous opioids (Racz et al. 2008). Future studies will examine the potential for B6 strain differences in basal and druginduced endogenous opioid levels as a potential neurochemical mechanism for variation in motivational behaviors. "
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    • "E2 may modulate the behavioral effects of cocaine by regulating MOR and KOR signaling in mesocorticolimbic brain structures in female rats [135]. In addition, sex-dependent differences have been found in the intake of ethanol in the absence of β-endorphins in mice [136], and in the regulation of gonadal hormone, DOR binding, and MOR density in the hippocampus by prenatal exposure to morphine in rats [137,138]. "
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    • "In a family-based association study, among other SNPs, association of intron 1 SNPs (rs934778 and rs1009388) was found in a smaller subgroup of subjects with both alcohol and opioid dependence within European American (EA) families (Xuei et al., 2007). Also, an association of alcoholism with 3 POMC gene SNPs, among them rs934778, was reported for European population (Racz et al., 2008). A number of studies investigated association of kappa opioid receptor gene (OPRK1) SNPs with alcoholism and other addictions (rev in (Levran et al., 2012)). "
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