Deficit in beta-endorphin peptide and tendency to alcohol abuse

Zalewska-Kaszubska, Jadwiga; Czarnecka, E

doi:10.1016/j.peptides.2004.11.010

Cited by 34 publications

(17 citation statements)

References 55 publications

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“…The opioid-deficiency hypothesis argues that individuals at high risk for developing alcoholism may be so in part because of modified endorphinergic circuits (Gianoulakis 2004; Oswald and Wand 2004; Zalewska-Kaszubska & Czarnecka, 2005). For instance, some studies have demonstrated lower endorphin levels in animals or humans prone to high levels of EtOH intake (Dai et al 2005; Grisel et al 1999; Marinelli et al 2003; Williams et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Influence of β-Endorphin on anxious behavior in mice: interaction with EtOH

et al. 2008

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Rationale-The opioid peptide β-endorphin (β-E) is synthesized by the pro-opiomelanocortin gene in response to environmental stressors and alcohol administration and is implicated in the behavioral sequelae associated with these stimuli.Objectives-We sought to determine the influence of β-E on the stress response by evaluating basal measures of anxiety as well as on EtOH-induced anxiolytic behavior using transgenic mice that differ with respect to β-E.Methods-Anxious behavior was evaluated for male and female heterozygous, wild type, and β-E knockout mice using the Light-Dark Box and Plus Maze assays. Subsequent tests evaluated behavior 20 min after administration of intraperitoneal saline or EtOH (0.5, 1.0 and 1.5 g/kg).Results-We observed an inverse relationship between β-E levels and the percentage of entries into open arms of the Plus Maze as well as the time spent in either the open arms or the light compartment of the Light-Dark box during basal conditions, suggesting that this peptide normally inhibits anxious behavior. However, mice lacking β-E demonstrated an exaggerated anxiolytic response to EtOH in these assays.Conclusions-These data suggest that β-E moderates the response to stressful stimuli and supports the hypothesis that this peptide influences the behavioral effects of EtOH. KeywordsAddiction; Ethanol; Anxiety; Opioids; Mice; Transgenic; Self-Medication β-endorphin (β-E) is a 31 amino-acid peptide that is cleaved from the carboxyl terminus of the Proopiomelanocortin (POMC) gene. As a member of the large family of opioid peptides that are widely and differentially distributed throughout the nervous system, it has been implicated in a variety of behaviors including the regulation of pain and reward, as well as in modulating neurocircuitry involved in learning and memory, motivation and processes associated with stress, fear or anxiety (e.g. Bloom 1980). The response to stressors involves a complex cascade of endocrine, autonomic and behavioral changes that seem to be generally aimed at maintaining or restoring homeostasis. At least in part because of its complexity, neither a precise definition nor thorough knowledge of the neurobiological underpinnings of the stress response has been elucidated (Pacak and Palkovitis 2001). Nonetheless, nearly any operational understanding includes activation of the hypothalamic-pituitary-adrenal (HPA) axis. This reaction involves Correspondence to: Judith E. Grisel, judy.grisel@furman.edu. NIH Public AccessAuthor Manuscript Psychopharmacology (Berl). Author manuscript; available in PMC 2010 February 9. The most well-studied effect of β-E is its ability to modulate pain, but an early report by Fratta et al. (1981) suggested that central administration of β-E produced opposite effects to that of ACTH administration ("reciprocal antagonism") on several behaviors in rats including cataplexy, rigidity and analgesia, and supported the notion that β-E is directly implicated in the homeostatic regulation of ACTH response. Indeed, β-E synthesis and release is prec...

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Section: Discussionmentioning

confidence: 99%

Influence of β-Endorphin on anxious behavior in mice: interaction with EtOH

et al. 2008

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“…SIB in their monkeys might have some parallels with alcoholism. The mu-opioid receptor plays a role in regulating the effects of alcohol, and alcohol consumption increases levels of βE, probably through increased release of POMC [58]. Compared to a lowrisk group, humans at high risk for developing alcoholism, have lower levels of βE and increased plasma βE in response to small doses of ethanol [58].…”

Section: Positive Versus Negative Associations Between Beta-endorphinmentioning

confidence: 99%

“…The mu-opioid receptor plays a role in regulating the effects of alcohol, and alcohol consumption increases levels of βE, probably through increased release of POMC [58]. Compared to a lowrisk group, humans at high risk for developing alcoholism, have lower levels of βE and increased plasma βE in response to small doses of ethanol [58]. Some macaques have an allele of the mu-opioid receptor gene that produces more than three times the affinity for βE, i.e., for a given level of βE, greater βE binding produces increased opioid effects in the body [28].…”

Section: Positive Versus Negative Associations Between Beta-endorphinmentioning

confidence: 99%

Beta-endorphin levels in longtailed and pigtailed macaques vary by abnormal behavior rating and sex

et al. 2007

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Frequent or severe abnormal behavior may be associated with the release of endorphins that positively reinforce the behavior with an opiate euphoria or analgesia. One line of research exploring this association involves the superhormone, proopiomelanocortin (POMC). The products of POMC appear to be dysregulated in some human subjects who exhibit self-injurious behavior (SIB). Macaque monkeys have POMC very similar to humans, and some laboratory macaques display SIB or frequent stereotypies. We investigated associations between plasma levels of three immunoreactive POMC fragments with possible opioid action and abnormal behavior ratings in macaques. In 58 adult male and female macaques (24 Macaca fascicularis and 34 M. nemestrina), plasma levels of intact beta-endorphin (βE) and the N-terminal fragment (BEN) were significantly higher in animals with higher levels of abnormal behavior. The C-terminal fragment (BEC) was significantly higher in males but unrelated to ratings of abnormal behavior. Levels of ACTH, cortisol, and (βE-ACTH)/βE dysregulation index were unrelated to abnormal behavior. None of the POMC products differed significantly by subjects' species, age, or weight. The finding that intact betaendorphin is positively related to abnormal behavior in two species of macaque is consistent with some previous research on human subjects and nonprimates. The positive relation of the N-terminal fragment of βE to abnormal behavior is a new finding.

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“…The present findings support the contention that the opioid peptide β-E plays a critical role in the neural substrates of alcohol reinforcement and addiction. Along this line, EtOH self-administration in animals depends upon this peptide (Grisel et al, 1999; Williams et al, 2007; Racz et al, 2008; but also see Grahame et al, 1998) and clinical studies have associated β-E levels with liability toward alcohol use disorders (Gianoulakis et al, 1989; Wand et al, 2001; Zalewska-Kaszubska and Czarnecka, 2004). …”

Section: Discussionmentioning

confidence: 99%

Locomotor sensitization to EtOH: contribution of β-Endorphin

Dempsey¹,

Grisel²

2012

Front. Mol. Neurosci.

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Alcohol use disorders, like all drug addictions, involve a constellation of adaptive changes throughout the brain. Neural activity underlying changes in the rewarding properties of alcohol reflect changes in dopamine transmission in mesolimbic and nigrostriatal pathways and these effects are modulated by endogenous opioids such as β-Endorphin. In order to study the role of β-Endorphin in the development of locomotor sensitization to repeated EtOH exposure, we tested transgenic mice that vary in their capacity to synthesize this peptide as a result of constitutive modification of the Pomc gene. Our results indicate that mice deficient in β-Endorphin show attenuated locomotor activation following an acute injection of EtOH (2.0 g/kg) and, in contrast to wildtype mice, fail to demonstrate locomotor sensitization after 12 days of repeated EtOH injections. These data support the idea that β-Endorphin modulates the locomotor effects of EtOH and contributes to the neuroadaptive changes associated with chronic use.

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Deficit in beta-endorphin peptide and tendency to alcohol abuse

Cited by 34 publications

References 55 publications

Influence of β-Endorphin on anxious behavior in mice: interaction with EtOH

Influence of β-Endorphin on anxious behavior in mice: interaction with EtOH

Beta-endorphin levels in longtailed and pigtailed macaques vary by abnormal behavior rating and sex

Locomotor sensitization to EtOH: contribution of β-Endorphin

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