Alcohol challenges in young men from alcoholic pedigrees and control families: a report from the COGA project.

Schuckit, Marc A.; Tsuang, John; Anthenelli, Robert M.; Tipp, Jayson E.; Nürnberger, John I.

doi:10.15288/jsa.1996.57.368

Cited by 127 publications

(77 citation statements)

References 18 publications

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“…Alcoholism risk has been associated with a low level of response to alcohol, as measured by subjective feelings of intoxication following an alcohol challenge (Schuckit, 1984(Schuckit, , 1994Bauer and Hesselbrock, 1993;Schuckit et al, 1996). A family history of alcoholism has also been associated with a diminished response to alcohol in nonalcoholics (Moss et al, 1989;O'Malley and Maisto, 1985;Pollock et al, 1986;Savoie et al, 1988;Schuckit, 1984;Schuckit et al, 2000;cf.…”

Section: Discussionmentioning

confidence: 99%

GABRA2 Alleles Moderate the Subjective Effects of Alcohol, Which are Attenuated by Finasteride

Pierucci‐Lagha

Covault

Feinn

et al. 2005

Neuropsychopharmacol

133

109

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GABA A receptors are involved in the subjective effects of alcohol. Endogenous neuroactive steroids interact with GABA A receptors to mediate several behavioral effects of alcohol in rodents. Based on a haplotypic association of alcohol dependence with the gene encoding the GABA A receptor a-2 subunit (GABRA2), we examined whether GABRA2 alleles are associated with the subjective response to alcohol. We also examined whether finasteride (a 5-a steroid reductase inhibitor), which blocks the synthesis of some neuroactive steroids, reduces the subjective response to alcohol. In all, 27 healthy social drinkers (15 males) completed a randomized, double-blind, placebo-controlled study of high-dose finasteride. After being pretreated with study drug, subjects consumed three alcoholic drinks. Subjective effects were measured repeatedly over the ascending blood alcohol curve. To examine the moderating role of genetic variation in GABRA2, a single-nucleotide polymorphism that was informative in association studies was included as a factor in the analysis. Subjects homozygous for the more common A-allele (n ¼ 7) showed more subjective effects of alcohol than did individuals with one or two copies of the alcohol dependence-associated G-allele (n ¼ 20, including two homozygotes). Among the A-allele homozygotes, there was a greater reduction in several subjective effects during the finasteride session compared to the placebo session. These findings provide preliminary evidence that the risk of alcoholism associated with GABRA2 alleles may be related to differences in the subjective response to alcohol. The effects of finasteride provide indirect evidence for a mediating role of neuroactive steroids in some of the subjective effects of alcohol.

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Section: Discussionmentioning

confidence: 99%

GABRA2 Alleles Moderate the Subjective Effects of Alcohol, Which are Attenuated by Finasteride

Pierucci‐Lagha

Covault

Feinn

et al. 2005

Neuropsychopharmacol

133

109

View full text Add to dashboard Cite

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“…Prior studies have shown that high-risk individuals, by virtue of a positive biological family history of alcoholism, show alterations in HPA axis response to a variety of behavioral and physiological agents (Peterson et al 1996;Gianoulakis et al 1996;King et al 1998;Schuckit et al , 1996Waltman et al 1994). Also, several recent studies have demonstrated that opioidergic hypothalamic sensitivity is greater in high-risk, FHϩ persons (Wand et al 1998(Wand et al , 2001) and may vary as a function of gender (Wand et al 1999a) and degree of obsessive-compulsive symptomatology (Mangold et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic-Pituitary-Adrenocortical (HPA) Axis Response and Biotransformation of Oral Naltrexone Preliminary Examination of Relationship to Family History of Alcoholism

King

Schluger

Gunduz

et al. 2002

Neuropsychopharmacology

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We examined HPA axis response to 50 mg oral naltrexone compared with placebo in 17 healthy male and female nonalcoholic subjects, approximately half of whom had a positive family history of alcoholism (FH ϩ ) and half of whom who did not (FH Ϫ)The endogenous opioid system plays a role in the modulation of the hypothalamic-pituitary-adrenal (HPA) axis (Cushman and Kreek 1974;Johnson et al. 1992;Kreek 1972Kreek , 1973Kreek , 1978. Opioid antagonist administration blocks the tonic opioid inhibition of HPA axis activity, thereby resulting in release of POMC-derived hormones in the pituitary and cortisol from the adrenal gland. Indeed, numerous studies have demonstrated acute increases in adrenocorticotropin (ACTH) and cortisol levels in man after intravenous infusion of the opioid antagonists naloxone (Cohen et al. 1983;Conaglen et al. 1985;Delitala et al. 1994;Naber et al. 1981;Martin del Campo et al. 1994;Morley et al. 1980;Schluger et al. 1998;Volavka et al. 1979a) and nalmefene . However, few studies have examined acute neuroendocrine response to the opioid antagonist naltrexone, which, in contrast to naloxone and nalmefene, is not available for intravenous administration.The two published studies on the acute HPA axis effects of orally administered naltrexone have both been conducted with relatively small sample sizes (n р 10). NO . 6 Naltrexone, HPA Axis, and Biotransformation 779The first study (Volavka et al. 1979b), conducted in ten normal male subjects, showed that oral naltrexone significantly increased cortisol levels two hours after administration and directionally (but nonsignificantly) increased ACTH levels one hour after administration. However, due to the small sample studied, the power may not have been sufficient to detect differences. The results may also have been confounded by the co-occurrence of pain sensitivity testing (i.e., 2-min cold pressor task) during the protocol, which may have produced independent HPA axis responses. A more recent study in six abstinent alcoholic patients (Farren et al. 1999) showed significant increases in cortisol and ACTH to three doses of oral naltrexone (25, 50, and 100mg) with no dose-dependent effects (Farren et al. 1999). It has been hypothesized that alterations in HPA axis function may play a role in various stages of addiction, including initiation, maintenance, and relapse (Kreek 1992). Naltrexone (50 mg oral) has shown efficacy in the treatment of alcohol dependence (Volpicelli et al. 1992(Volpicelli et al. , 1997O'Malley et al. 1992;Anton et al. 1999), which led to its FDA-approval for adjunctive treatment of alcoholism. Studies examining HPA axis response after oral naltrexone administration might be of potential clinical relevance as neuroendocrine changes and sensitivity to naltrexone could relate to individual differences and treatment response. Hypothetically, the effects of an opioid antagonist, such as naltrexone, in modulating tonic inhibition of the opioid system at various receptors, including primarily , but also ␦ and , may relate to tr...

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“…The degree of subjective response to alcohol is a substantial contributor to the risk for problematic drinking. Individuals who experience enhanced positive responses or reduced negative responses to alcohol are at increased risk for subsequent development of AUD (Schuckit et al, 1996;Erblich et al, 2001). Some reports suggest that schizophrenia patients use alcohol to 'self-medicate' psychotic symptoms, subjective distress, insomnia, social anxiety, or medication side effects, whereas other studies suggest that subjects with schizophrenia use alcohol for its stimulatory or euphoric effects (Noordsy et al, 1991;Chambers et al, 2001;Green, 2005).…”

Section: Introductionmentioning

confidence: 99%

Enhanced Sensitivity to the Euphoric Effects of Alcohol in Schizophrenia

D’Souza

Gil

Madonick

et al. 2006

Neuropsychopharmacol

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The purpose of this study was to determine whether schizophrenia was associated with alterations in alcohol response that might explain the elevated risk for AUDs in this population. In a randomized, double-blind, placebo-controlled, counter-balanced 3 test day laboratory study, the effects of alcohol were compared in 23 subjects with schizophrenia (without any previous alcohol use disorder (AUD) but with some alcohol exposure) and in 14 healthy subjects matched for age, gender, education, and lifetime exposure to alcohol. Standard alcohol drinks in a scheduled design were administered to produce blood alcohol levels of 0, 0.02-0.04 mg%, or 0.06-0.08 mg%. Schizophrenia symptoms, perceptual alterations, stimulant and depressant subjective effects of alcohol, and 'high' were measured before alcohol administration and at several post-drug time points. Verbal learning and recall, vigilance and distractibility, and motor function were assessed once per test day. Relative to healthy subjects, subjects with schizophrenia reported greater euphoria and stimulatory effects in response to alcohol. Alcohol produced small transient increases in positive psychotic symptoms and perceptual alterations without affecting negative symptoms. Alcohol also impaired several aspects of immediate and delayed recall, and vigilance, and distractibility. Schizophrenia patients showed increased euphoric and stimulatory responses to alcohol. These exaggerated positive responses to alcohol doses may contribute to the increased risk for AUDs associated with schizophrenia. The absence of 'beneficial' effects of alcohol does not support a self-medication hypothesis of alcohol use in schizophrenia.

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Alcohol challenges in young men from alcoholic pedigrees and control families: a report from the COGA project.

Cited by 127 publications

References 18 publications

GABRA2 Alleles Moderate the Subjective Effects of Alcohol, Which are Attenuated by Finasteride

GABRA2 Alleles Moderate the Subjective Effects of Alcohol, Which are Attenuated by Finasteride

Hypothalamic-Pituitary-Adrenocortical (HPA) Axis Response and Biotransformation of Oral Naltrexone Preliminary Examination of Relationship to Family History of Alcoholism

Enhanced Sensitivity to the Euphoric Effects of Alcohol in Schizophrenia

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