The Opioid Peptides Enkephalin and β-Endorphin in Alcohol Dependence

Abstract

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

Involvement of Activated Brain Stress Responsive Systems in Excessive and “Relapse” Alcohol Drinking in Rodent Models: Implications for Therapeutics

“…The POMC deficiency affects female mice more strongly than males, suggesting that POMC may influence alcohol consumption in a sex-specific manner [Zhou et al, JPET #245621R3 2017b]. Our result is in line with early studies demonstrating a decreased alcohol intake in betaendorphin and MOP-r knockout mice with more notable differences in females [Hall et al, 2001;Racz et al, 2008] (Table 2). Sex differences have also been observed in a human genetic study, showing that the Pomc two-marker haplotype is associated with alcoholism only in women [Racz et al, 2008].…”

“…Our result is in line with early studies demonstrating a decreased alcohol intake in betaendorphin and MOP-r knockout mice with more notable differences in females [Hall et al, 2001;Racz et al, 2008] (Table 2). Sex differences have also been observed in a human genetic study, showing that the Pomc two-marker haplotype is associated with alcoholism only in women [Racz et al, 2008]. These results also contribute to the idea that there are sex differences in opioid regulation of alcohol dependence [Becker and Koob, 2016].…”

“…Consistent with previous studies in mice [Hall et al, 2001;Racz et al, 2008;Hwa et al, 2011;Yoo et al, 2012] and rats (recently reviewed by Becker and Koob 2016), we confirm sex differences in alcohol drinking, with higher alcohol intake in females. The genotype differences in alcohol intake between hypothalamic POMC deficient and wildtype mice are much greater in females than in males.…”

“…It was not clear, however, whether there is an involvement of β-endorphin in regulation of alcohol drinking, as earlier studies using β-endorphin deficient mice show inconsistent results by different groups [Grisel et al, 1999;Grahame et al, 2000;Racz et al, 2008] (Table 2) deficiency resulting from selective deletion of Pomc enhancers [Lam et al, 2015]. Specifically, we determine the effect of tissue-specific Pomc gene manipulation on: (a) "binge" drinking in a DID model [Rhodes et al, 2005]; (b) acquisition and escalation of excessive alcohol drinking in a chronic intermittent access (IA) model [Wise, 1973;Simms et al, 2008;Hwa et al, 2011], and (c) "relapse" drinking in an alcohol deprivation effect (ADE) model in mice of both sexes [Holter and Spanagel, 1999;Heyser et al, 2003].…”

Sex differences in binge‐like EtOH drinking, corticotropin‐releasing hormone and corticosterone: effects of β‐endorphin

“…In the clinic, basal levels of plasma β-E, as well as a rise in this peptide following alcohol administration, correlate with a heritable risk for high consumption (Dai et al 2005;Kiefer et al 2006). Our laboratory and others have demonstrated that β-Edeficient mice exhibit altered patterns of EtOH consumption, which depend upon sex (Williams et al 2007;Zhou et al 2017), and a Pomc haplotype marker has been associated with human alcoholism in women, but not men (Racz et al 2008). However, the mechanisms responsible for this interaction remain unknown.…”