Enhanced Sensitivity of Pituitary βEndorphin to Ethanol in Subjects at High Risk of Alcoholism

Gianoulakis, Christina; Krishnan, Brinda; Thavundayil, Joseph

doi:10.1001/archpsyc.1996.01830030072011

Cited by 216 publications

(142 citation statements)

References 51 publications

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“…Indeed, it was this basic work that led to the hypothesis that naltrexone might be clinically useful in treating alcohol dependence, hence the development of naltrexone is a good example of translational neuroscience. Examining the effects of alcohol consumption and naltrexone in high-risk individuals has further supported the idea that there may be a relative lack of basal b-endorphin release and that the opioid system is more sensitive to alcohol among high-risk subjects (Gianoulakis, 1996;Gianoulakis et al, 1996). Subjectively, some fraction of the rewarding effects of alcohol ingestion in high-risk subjects can be blocked by naltrexone (King et al, 1997).…”

Section: Table 1 Baseline Demographics and Clinical Characteristics Omentioning

confidence: 90%

A Functional Polymorphism of the μ-Opioid Receptor Gene is Associated with Naltrexone Response in Alcohol-Dependent Patients

Oslin

Berrettini

Kranzler

et al. 2003

Neuropsychopharmacol

550

399

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This study examined the association between two specific polymorphisms of the gene encoding the m-opioid receptor and treatment outcomes in alcohol-dependent patients who were prescribed naltrexone or placebo. A total of 82 patients (71 of European descent) who were randomized to naltrexone and 59 who were randomized to placebo (all of European descent) in one of three randomized, placebo-controlled clinical trials of naltrexone were genotyped at the A +118 G (Asn40Asp) and C +17 T (Ala6Val) SNPs in the gene encoding the m-opioid receptor (OPRM1). The association between genotype and drinking outcomes was measured over 12 weeks of treatment. In subjects of European descent, individuals with one or two copies of the Asp40 allele treated with naltrexone had significantly lower rates of relapse (p ¼ 0.044) and a longer time to return to heavy drinking (p ¼ 0.040) than those homozygous for the Asn40 allele. There were no differences in overall abstinence rates (p ¼ 0.611), nor were there differences in relapse rates or abstinence rates between the two genotype groups among those assigned to placebo. These preliminary results are consistent with prior literature demonstrating that the opioid system is involved in the reinforcing properties of alcohol and that allelic variation at OPRM1 is associated with differential response to a m-receptor antagonist. If replicated, these results would help to identify alcohol-dependent individuals who may be most likely to respond to treatment with naltrexone.

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Section: Table 1 Baseline Demographics and Clinical Characteristics Omentioning

confidence: 90%

A Functional Polymorphism of the μ-Opioid Receptor Gene is Associated with Naltrexone Response in Alcohol-Dependent Patients

Oslin

Berrettini

Kranzler

et al. 2003

Neuropsychopharmacol

550

399

View full text Add to dashboard Cite

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“…Concerning the activity of the hypothalamic-pituitary-adrenal (HPA) system, lower levels of adrenocorticotropin (ACTH; Schuckit et al, 1988) and cortisol (Schuckit et al, 1987) were found after ingestion of the rather high dosage of 0.88 g/kg ethanol in sons of alcoholics compared to control males, while this difference was not apparent after 0.6 g/kg in the same studies. Another study found no cortisol changes after ingestion of 0.25, 0.5, and 0.75 g/kg ethanol, while a rise in b-endorphin after the medium and high dose was observed in offspring of alcoholics but not in control subjects (Gianoulakis et al, 1996). Stimulation of the HPA system by i.v.…”

Section: Introductionmentioning

confidence: 96%

Effect of Ethanol on Hypothalamic–Pituitary–Adrenal System Response to Psychosocial Stress in Sons of Alcohol-Dependent Fathers

Zimmermann

Spring

Kunz-Ebrecht

et al. 2004

Neuropsychopharmacol

104

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Familial risk and environmental stress promote the development of alcohol dependence. This study tested two hypotheses: that a family history for alcoholism is associated with (i) a greater stress response and (ii) more effective stress response dampening by alcohol. We studied 29 high-risk subjects with a paternal history of alcoholism (PHA) and 23 family history negative (FHN) controls all aged 18-26 years, who were recruited using a representative sample of the local area population. Psychosocial stress was induced by having subjects deliver a speech and perform mental arithmetics in front of an audience on two separate days, after drinking either placebo or alcohol (0.6 g/kg) in a randomized double-blind crossover design. Plasma cortisol and adrenocorticotropin (ACTH) were measured up to 90 min after the test. The stress task induced a phasic increase of both hormones in PHA and FHN subjects during all experimental conditions except in tests where FHN subjects received alcohol during the second day. ACTH secretion was higher in PHA subjects during placebo experiments, but equal to controls after alcohol administration. The alcohol-induced attenuation of ACTH response was statistically significant in PHA, but not FHN, subjects. Cortisol response was higher in PHA than FHN probands if placebo was administered during the first test, but equal if subjects received alcohol first. The increased stress response and its stronger dampening by alcohol in sons of alcoholic fathers suggest a mechanism by which predisposition to develop alcohol use disorders might be expressed, implying that a transient favorable alcohol effect might occur in PHA, but not FHN, subjects.

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“…Furthermore, unaffected adult children of alcoholics have basal levels of ␤ -endorphin comparable to those of abstinent alcoholics and significantly lower than those of unaffected adults without a parental history of alcoholism (Gianoulakis et al 1989(Gianoulakis et al , 1996. When given alcohol, adult children of alcoholics also showed a significantly greater increase (i.e., a "normalization") of ␤ -endorphin levels (Gianoulakis et al 1989(Gianoulakis et al , 1996.…”

mentioning

confidence: 98%

Naltrexone vs. Nefazodone for Treatment of Alcohol Dependence A Placebo-Controlled Trial

Kranzler

Modesto‐Lowe

Kirk

2000

Neuropsychopharmacology

204

122

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Enhanced Sensitivity of Pituitary βEndorphin to Ethanol in Subjects at High Risk of Alcoholism

Abstract: This study indicates that the pituitary beta-endorphin system, but not the adrenal cortisol system, of the HR subjects shows an enhanced sensitivity to ethanol, which may be an important factor in controlling ethanol consumption.

Cited by 216 publications

References 51 publications

A Functional Polymorphism of the μ-Opioid Receptor Gene is Associated with Naltrexone Response in Alcohol-Dependent Patients

A Functional Polymorphism of the μ-Opioid Receptor Gene is Associated with Naltrexone Response in Alcohol-Dependent Patients

Effect of Ethanol on Hypothalamic–Pituitary–Adrenal System Response to Psychosocial Stress in Sons of Alcohol-Dependent Fathers

Naltrexone vs. Nefazodone for Treatment of Alcohol Dependence A Placebo-Controlled Trial

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