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PubMed1983

Effect of prenatal alcohol exposure on consumption of alcohol and alcohol-induced sleep time in mice.

An animal model was used to examine the effect of maternal alcohol administration on behaviors in the offspring which might predispose to alcoholism. Pregnant C3H mice were administered a liquid diet containing 28% ethanol-derived calories (EDC) from Gestation-Day 8 until parturition. Control animals were either pair-fed an isocaloric 0% EDC diet or received standard lab chow and water throughout pregnancy. Offspring were tested for sleep time following a challenge dose of 3.5 or 4.5 g/kg ethanol at 25 or 110 days of age or for consumption of 10% w/v ethanol in a two-bottle choice situation. The results demonstrated that prenatal exposure to alcohol did not affect alcohol-induced sleep time at either testing age or dose and that waking blood alcohol levels were similar across groups. Voluntary alcohol consumption, however, was higher in mice exposed to alcohol in utero during the initial week of testing but intake decreased to near control levels by the third week. Whether other alcohol-related behaviors are altered by prenatal alcohol exposure remains to be examined.

Alcohol Drinking↗
PubMed1984

The MacAndrew Alcoholism Scale: severity of alcohol abuse and parental alcoholism.

The MacAndrew Alcoholism Scale (MAC), an empirically derived MMPI scale, appears to measure a relatively stable trait common to many alcoholics. The present study examined the relationship between the MAC and two potentially important sources of variation within an alcoholic population, severity of alcohol abuse and history of parental alcoholism. Study participants included 105 consecutive admissions to an alcoholism day treatment program. For both male and female patients, scores on the MAC were found to correlate with the severity of alcohol abuse and factor analytically derived subscales of the MAC were found to differentiate alcoholics with and without a history of parental alcoholism.

Adult↗
PubMed1999

Modeling of alcohol use mediates the effect of family history of alcoholism on adolescent alcohol expectancies.

The relative impact of biological family history of alcoholism and exposure to abusive parental drinking on alcohol effect expectancies of adolescent offspring were investigated in the present study. Exposure to familial models of alcohol abuse and biological family history were both predictive of positive alcohol effect expectancies of adolescent offspring. Degree of exposure to an alcohol-abusing family member mediated the relationship between biological family history of alcoholism and adolescent alcohol outcome expectancies. These results support prior findings of expectancy differences between youths with and without a family background of alcoholism and provide evidence supporting the significance of family modeling influences in the development of adolescents' alcohol expectancies.

Adolescent↗
PubMed1987

Depression and alcohol consumption in non alcoholic and alcoholic women. A clinical study.

The relationship between level of depression and alcohol consumption was studied in 64 alcoholic women, 80 non alcoholic female psychiatric patients and 72 healthy women, using a clinical, semistructured interview, SADS, SSP and HSCL-58. Among DSM-III depressive women, the alcohol consumption was bimodally distributed. Among healthy women, there was an inverse relationship between depressive symptoms and alcohol consumption. Among non alcoholic women dysthymic patients consumed significantly more than major depressive, subclinically depressed and psychotic non depressive patients, and significantly less than healthy, non depressive women. Among alcoholic women, there was no difference in consumption between major depressives, dysthymics and the other diagnostic groups. The results show that there was no general dose-response relationship between level of depression and alcohol consumption. Anxiety level and personality disorder may be more influential on the alcohol consumption than the level of depression among depressive women.

Adolescent↗
PubMed1993

Heart-rate reactivity and alcohol consumption among sons of male alcoholics and sons of non-alcoholics.

Recent studies have demonstrated that sons of male alcoholics with multigenerational family histories of male alcoholism are characterized by sober heart-rate hyperreactivity to aversive stimuli, susceptibility to alcohol-induced dampening of that hyperreactivity and by increased resting heart rate while intoxicated. Regression analyses indicate that the magnitude of alcohol-induced change in resting and reactive cardiac response is significantly and powerfully associated with the degree of self-reported voluntary alcohol consumption among 85 non-alcoholic males who are either lacking or who have moderate or extensive family histories of male alcoholism. It appears that heightened sensitivity to alcohol-induced increase in resting and decrease in reactive heart rate might mark or underlie familial risk for developing alcoholism.

Adolescent↗
PubMed2006

The metabotropic glutamate 2/3 receptor agonist LY404039 reduces alcohol-seeking but not alcohol self-administration in alcohol-preferring (P) rats.

Metabotropic glutamate (mGlu) receptors have been shown to mediate a number of behaviors including emotionality and responsivity to stress as demonstrated by efficacy in preclinical and clinical studies. The objective of this study was to assess the effects of the mGlu2/3 receptor agonist LY404039 (LY) on operant ethanol (EtOH) self-administration during alcohol seeking (pavlovian spontaneous recovery, PSR), alcohol relapse (alcohol deprivation effect, ADE), and maintenance responding for alcohol. Adult alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15% EtOH (v/v) and water on a concurrent fixed-ratio 5-fixed-ratio 1 (FR5-FR1) schedule of reinforcement in daily 1h sessions. After at least 10 weeks of daily 1 h sessions, rats underwent seven extinction sessions, followed by 2 weeks of no manipulation, and then rats were tested for the expression of an EtOH PSR for four sessions. Rats were then given a week in their home cage before being returned to the operant chambers with access to EtOH and water (alcohol relapse). Finally, the effects of LY upon maintenance EtOH and water responding were assessed once stable responding was reestablished. The mGlu2/3 receptor agonist LY404039 reduced responding on the EtOH in the PSR test. LY also reduced the expression of an alcohol deprivation effect (ADE) during relapse, but did not reduce EtOH responding under maintenance conditions. The results of this study demonstrate that activating mGlu2/3 receptors inhibits the expression of alcohol seeking and relapse behavior without altering alcohol self-administration behavior.

Alcohol Drinking↗
PubMed2006

Baclofen-induced suppression of alcohol deprivation effect in Sardinian alcohol-preferring (sP) rats exposed to different alcohol concentrations.

This study investigated the effect of the gamma-aminobutyric acid(B) (GABA(B)) receptor agonist, baclofen, on alcohol deprivation effect (the transient increase in alcohol intake occurring after a period of alcohol abstinence) in Sardinian alcohol-preferring (sP) rats exposed to 4 bottles containing water and 10%, 20%, and 30% (v/v) alcohol, respectively. Acute administration of baclofen (1 mg/kg, i.p.) suppressed both aspects of alcohol deprivation effect: the extra-intake of alcohol and the selection of the highest concentrated alcohol solution. These results suggest that the GABA(B) receptor is part of the neural substrate mediating alcohol deprivation in sP rats.

Alcohol Drinking↗
PubMed2000

Neonatal alcohol exposure produces more severe motor coordination deficits in high alcohol sensitive rats compared to low alcohol sensitive rats.

Prenatal exposure to alcohol can produce a number of behavioral alterations, including hyperactivity, learning deficits and motor impairments. However, the severity and nature of behavioral alterations varies markedly among children of women who drink during pregnancy. One important determinant of this variation may be genetic differences in the response to alcohol. Recently, we demonstrated that exposure to alcohol during development produced hyperactivity in rats bred for high alcohol sensitivity (HAS), but not in rats bred for low alcohol sensitivity (LAS). These lines were selectively bred for extremes in alcohol-induced "sleep time." The present study investigated the effects of ethanol exposure during development on motor coordination later in life in both HAS and LAS rats. Using an artificial rearing procedure, neonatal pups from each line were exposed to a binge-like alcohol treatment on postnatal days (PD) 4-9. Within each line, one group was exposed to ethanol (6.0 g/kg/day), one group served as an artificially reared control, and a third served as a normally reared control group. On PD 30, parallel bar motor performance was evaluated. Exposure to ethanol during development severely impaired motor performance in the HAS rats compared to their controls. In LAS rats, early ethanol exposure produced only mild and nonsignificant effects on motor performance. Thus, HAS rats were more vulnerable to ethanol-induced motor deficits compared to the LAS rats. Importantly, there were no differences in peak blood alcohol level between the lines, indicating that vulnerability to ethanol's teratogenic effects was not due to differences in metabolic rate. These results suggest that genetic differences in response to alcohol may serve as a predictor for susceptibility to ethanol's teratogenic effects.

Alcohol Drinking↗
PubMed1990

A comparison of primary alcoholics, secondary alcoholics, and nonalcoholic psychiatric patients on the MacAndrew Alcoholism Scale.

The MacAndrew Alcoholism (MAC) and Sc scales of the Minnesota Multiphasic Personality Inventory (MMPI) were examined in four groups of 20 male patients. Comparisons were made among primary alcoholics, secondary alcoholics (i.e., alcoholic psychiatric patients), nonalcoholic psychiatric patients (mixed diagnoses), and conservatively defined, nonalcoholic schizophrenics. Primary alcoholics scored higher on the MAC scale than did secondary alcoholics and other groups; schizophrenics scored lower than all other groups. Primary alcoholics were lower on the Sc scale than schizophrenics but did not differ from other groups. The results support MacAndrew's (1981) distinction between primary and secondary alcoholics and suggest that the MAC scale may enhance differentiation among diagnoses other than alcoholism.

Adult↗
PubMed1986

Variability in the effect of alcohol on alcohol metabolizing enzymes may determine relative sensitivity to alcohols: a new hypothesis.

Individual and racial differences in response to alcohol and with respect to alcoholism have strong genetic predispositions. Most studies on the actual genetic determinants have concentrated on the isozymes of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), the two enzymes of the primary pathway of alcohol metabolism. Although few "activity" variants (associated with mutations in the structural genes) of the two enzymes are known to exist in susceptible groups, these observations do not offer an adequate explanation for the observed variability in response to alcohols in the population. Some recent studies have reported alterations in the specific activity of the two enzymes following exposure to alcohol for different lengths of time in man, rat, and mice. The induction-repression so observed is hypothesized to be regulated by one or more inducibility genetic elements (IGE) associated with the structural loci of the two enzymes. Variability in IGE will permit a genotype (individual) specific response in ADH and ALDH specific activity when challenged with a given level of alcohol. Considering the relative toxicity of acetaldehyde, the primary metabolite of this pathway, the resistant individuals would be expected to show ALDH induction. Conversely, the susceptible individuals should respond to alcohol by ALDH repression. The ability of an individual to show induction or repression following alcohol ingestion will depend on his or her IGE genotype(s) associated with specific enzyme loci. Also, the degree of polymorphism at these loci would be expected to be extensive and yet population and race specific. Once experimentally established, this approach could have important implications in screening, counselling, prevention, and in novel approaches to treatment.

Alcohol Dehydrogenase↗
PubMed2000

Alcohol use in the year before marriage: alcohol expectancies and peer drinking as proximal influences on husband and wife alcohol involvement.

BACKGROUND: Models of adolescent alcohol involvement that include individual difference, family, and peer risk factors indicate a significant association between the drinking of adolescents and that of their peers. Peer drinking influences, however, have not been investigated extensively in integrative models of adult drinking. The purpose of this study was to test a model of adult drinking that incorporated the potentially important risk factor of partner drinking and in which proximal risk factors (peer drinking, alcohol expectancies) were hypothesized to be strongly associated with adult alcohol use and to mediate relationships between more distal risk factors and drinking. METHODS: Couples (n = 389) were assessed at the time of their first marriage. Separate, self-administered questionnaires were completed at home by both husbands and wives. Distal risk factors included family history of alcoholism, antisocial behavior, and depressive symptomatology. Substantive relationships were tested in a model that included spousal associations with respect to distal risk factors, proximal risk factors, and drinking. RESULTS: Findings demonstrate the unique association of alcohol expectancies and peer drinking with adult alcohol use. Of particular relevance is the significance of the social network as a correlate of adult drinking. A peer network characterized by a higher level of alcohol involvement was strongly associated with heavier drinking among both men and women. This relationship was independent of sociodemographic and individual difference factors, alcohol expectancies, and partner's drinking. Results also demonstrate the similarity between husband and wife drinking, an association that cannot be attributed to assorting with respect to the other risk factors. CONCLUSIONS: The social network continues to significantly impact drinking behavior in adulthood. The relevancy of peer and partner drinking influences to adult alcohol involvement suggests that the immediate social environment may have a prominent role in the continuity/discontinuity of heavy or problem drinking during the transition to marriage.

Adult↗
PubMed1994

Monoamine oxidases and alcoholism: studies in unrelated alcoholics, normal controls and alcoholic families.

Monoamine oxidases (A and B) are of great interest in connection with alcoholism. Low MAO activity has been found in the brains and the platelets of alcoholics and their relatives supporting the hypothesis that low MAO activity is a biological marker for vulnerability to misuse. In order to determine the role of the MAO genes in alcoholism we have measured MAO-B activity and typed two simple sequence repeats (one in the MAO-A gene and one in the MAO-B gene) in a sample of 133 unrelated alcoholics, 300 subjects from 30 two- and three-generation pedigrees ascertained through an alcoholic proband, and 92 normal controls. The unrelated alcoholic group did not differ in MAO-B activity from normal controls nor were there significant differences between subtypes. We did, however, find significant differences between alcoholic males and females (t = 2.836, p = .005), a difference that was not present in controls. A two-way analysis of variance of MAO-B activity as a function of the allelic variation of each marker locus and diagnosis among male subjects was performed. There was no evidence for mean differences in activity levels for different alleles. The distribution of MAO-A and MAO-B "alleles" in the alcoholic sample differed from that of the control sample. Affected sib pair linkage analysis of MAO genes and alcoholism showed no evidence for an excess of concordant affected sib pairs suggesting that this region of the X-chromosome does not harbor a susceptibility locus.

Adult↗
PubMedDate not supplied

Meta-analysis of the effects of alcohol dehydrogenase genotype on alcohol dependence and alcoholic liver disease.

The purpose of this paper is to assemble and evaluate existing data on the effect of genetic variation in ADH2 and ADH3 on the risk of alcohol dependence, and on the risk of alcoholic liver disease. Calculations of odds ratios and their confidence limits, and tests for heterogeneity of the results from the available studies, have been performed. It is clear that possession of the ADH2-2 allele decreases the risk of alcohol dependence, but it increases the risk of alcoholic liver disease among alcoholics. ADH3 variation also has significant effects on alcohol dependence, which may be due to linkage to ADH2; the ADH3 effect differs significantly between Asian and European subjects. Therefore ADH genotype has substantial effects on risk of alcohol dependence and alcoholic liver disease, but more work is needed on the generalizability of these findings to non-Asian populations, and on possible mechanisms.

Alcohol Dehydrogenase↗
PubMed1996

Alcohol dementia and alcohol delirium in aged alcoholics.

In the present study, 126 alcoholics aged 60 years or older were compared with 104 alcoholics aged 35-45 years. No dementia was found in the younger group, whereas 62.7% of the aged patients had dementia; the dementia being irreversible in 32.9% of such patients. Cases of so-called alcohol dementia excluding organic brain diseases accounted for 42.1%. The percentage of aged alcoholics having dementia increased with age, being far beyond the frequency of senile dementia in the general aged. Among various physical complications, hepatic injury and myocardiopathy were more frequent in the aged alcoholics than in general aged people, suggesting that hypertension, myocardiopathy and hepatic injury underlie the manifestation of dementia. There was no case of dementia attributable to the direct effect of alcohol distinctly exceeding the effects of various physical factors. Problem behaviors characteristic of the aged group included 'being soaked in drink' and being inebriated, showing no correlation with the presence or absence of dementia. There was no significant difference in frequency of delirium between the aged group and the younger group. However, in aged alcoholics delirium tended to continue for a longer period during abstinence and was more likely to occur even during non-abstinence. A similar trend was found in aged alcoholics with dementia compared with those without dementia.

Age Factors↗
PubMed2004

[Genetic polymorphisms of alcohol-metabolizing enzymes and cytokines in patients with alcohol induced pancreatitis and alcoholic liver cirrhosis].

BACKGROUND/AIMS: Susceptibility to organ damage induced by alcohol may be related to inherited variations (polymorphisms) in alcohol-metabolizing enzymes, or polymorphisms affecting cytokines. The aim of this study was to compare the genotype and allelic frequencies of ADH2, ADH3, ALDH2, cytochrome P450-2E1, IL-1, IL-6, IL-8 and tumor necrosis factor-alpha in patients with alcoholic pancreatitis and alcoholic liver cirrhosis with those of controls. METHODS: We determined the polymorphism of genes of the above-mentioned alcohol-metabolizing enzymes and cytokines in 29 alcoholic pancreatitis patients (AP), 22 alcoholic liver cirrhosis patients (LC) and 100 healthy blood donors (control). The genotypes were characterized by restriction fragment length polymorphism after amplification of genomic DNA by polymerase chain reaction. RESULTS: The allelic frequency of CYP2E1*c2 was significantly different in three groups (AP: LC: Control=0.224: 0.136: 0.320, p<0.05). There was no significant difference in the other genotypes or allelic frequencies of the three groups. The allelic frequencies of CYP2E1*c2 and ALDH2*2 were more frequent in the control than patients with alcoholic liver cirrhosis (LC: Control=0.136: 0.320, p<0.05, LC: Control= 0.114: 0.265, p<0.05). Allelic frequencies of ADH2 was statistically different between LC and control (ADH2*1; LC: Control=0.727: 0.495, ADH2*2; 0.227: 0.360, ADH2*3; 0.046: 0.145, p<0.05). CONCLUSIONS: There was no difference in the frequencies of genotype and allele of enzymes and cytokines among the three groups. However, frequency of ADH2*1 was significantly higher and those of CYP2E1*c2 and ALDH2*2 were significantly lower than LC group than control.

Adult↗
PubMed1998

Neonatal alcohol exposure produces hyperactivity in high-alcohol-sensitive but not in low-alcohol-sensitive rats.

Children of women who consume high amounts of alcohol during their pregnancies vary greatly in physical and behavioral outcomes. Although many factors, such as dose and timing of exposure, undoubtedly contribute to this variation, one important determinant may be genetic differences in the response to alcohol. The present study examined activity levels in high alcohol sensitivity (HAS) and low alcohol sensitivity (LAS) rats following neonatal alcohol exposure. These lines were selectively bred for extremes in ethanol-induced "sleep times." The HAS and LAS offspring were exposed to alcohol via an artificial rearing procedure using the "pup-in-the-cup" technique. Rat pups were exposed to ethanol (6 g/kg/day) from postnatal day (PD) 4 through 7 and faded to a dose of 3 g/kg/day on PD 8 and 9. An artificially reared gastrostomy control group (GC) and a normally reared suckle control group (SC) were also included. Activity level was measured on PD 18 through PD 21 for 30 min daily in automated activity monitors. Neonatal ethanol exposure produced overactivity in HAS rats, relative to their controls, but the same ethanol treatment had no effect on the LAS rats. Importantly, there were no differences in blood alcohol concentrations (around 420 mg/dl) between the two lines during the treatment period. These data suggest that genetic differences in response to alcohol may be a predictor for some of the behavioral teratogenic effects of alcohol.

Animals↗
PubMed1998

Formation and Degradation of Furfuryl Alcohol, 5-Methylfurfuryl Alcohol, Vanillyl Alcohol, and Their Ethyl Ethers in Barrel-Aged Wines.

Furfural, 5-methylfurfural, and vanillin co-occurred in 64 barrel-aged red, white, and model wines with the reduction products, furfuryl alcohol, 5-methylfurfuryl alcohol, and vanillyl alcohol, and with the corresponding ethyl ethers of these alcohols. Hydrolytic studies in a model wine have shown that 5-methylfurfuryl ethyl ether is formed rapidly from 5-methylfurfuryl alcohol, but both decomposed quickly under the conditions. Vanillyl ethyl ether was also formed relatively rapidly, and both this ether and vanillyl alcohol were stable in the model wine. The formation of furfuryl ethyl ether from furfuryl alcohol and the subsequent decomposition of these two compounds were comparatively slow. The relative concentration of these aromatic alcohols and ethers in the barrel-aged wines was consistent with the observed stability of the furan derivatives, but low concentrations of vanillyl alcohol and vanillyl ethyl ether observed in all samples showed that factors other than solvolytic degradation were responsible for reducing the concentration of these compounds in wine. Furfuryl ethyl ether, which had an aroma threshold of 430 µg/L in a white wine, was found at approximate concentrations of up to 230 µg/L in the wines.

Journal Article↗
PubMedDate not supplied

Response to alcohol in daughters of alcoholics: a pilot study and a comparison with sons of alcoholics.

Drinking, but not alcohol-dependent, 18-29-year-old daughters of alcoholics (n = 38) from the Collaborative Study on the Genetics of Alcoholism were compared to 75 family-history-positive (FHP) men from the same families, and 68 family-history-negative (FHN) male controls. Subjects received 0.75 ml/kg of ethanol (for women), 0.9 ml/kg of ethanol (for men), and placebo, each of which was consumed over 8 min on different occasions. The breath-alcohol concentrations (BrAC) and reactions to alcohol [using the Subjective High Assessment Scale (SHAS) and body sway measures] were evaluated over 210 min. The results indicate that, despite slightly higher BrAC values for the FHP men, on the SHAS the FHP women and the FHP men demonstrated significantly lower scores than the FHN male controls, although the values for FHP men and women did not differ. On body sway, the FHP men showed evidence of less alcohol-related increases than FHN men, and there was a trend in the same direction for FHP women, but only early in the session (e.g. at 60 min). Pilot data for 11 FHN women revealed higher scores for both SHAS and body sway at 60 min, compared to FHP women, but, perhaps reflecting the small number of subjects, the family history differences were not significant. Overall, the results in FHP women resemble those for FHP men, and suggest that a low level of response to alcohol might also be a characteristic of daughters of alcoholics.

Adolescent↗