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PubMed2003

Brain mitochondrial aldehyde dehydrogenase: relation to acetaldehyde aversion in low-alcohol-drinking (UChA) and high-alcohol-drinking (UChB) rats.

Previous reports indicate that the low-drinker (UChA) rats, when compared to high-drinker (UChB) rats, display lower mitochondrial aldehyde dehydrogenase (ALDH2) activity due to a mutation of the Aldh2 gene. Because a later study found line differences in sensitivity to the aversive effects of acetaldehyde (AcH) administered intraperitoneally (i.p.), which were not associated with the line difference detected in blood AcH levels, the present study examined the contribution of brain ALDH2 activity to AcH aversion in UChA and UChB rats. In experiment 1, we established the dose - response curves for AcH aversion (25, 50 or 100 mg/kg i.p.) in rats of both lines by using a conditioned taste aversion (CTA) paradigm. The results confirm our previous finding that UChA and UChB rats presented marked differences in their AcH aversion thresholds, which were not associated with the line differences detected in blood AcH levels. In experiment 2, the possibility that the inhibition of the brain ALDH2 would lower the AcH aversion threshold in both lines was studied by determining the effect of cyanamide (10 mg/kg i.p.) pretreatment, an inhibitor of ALDH, on AcH aversion, blood AcH levels and brain ALDH2 activity. The finding that blocking the brain ALDH2 (52%) by cyanamide can make a non-aversive dose of AcH (25 mg/kg) aversive to UChA and UChB rats at blood AcH levels comparable to those induced by a non-aversive dose of AcH (100 mg/kg) in control UChB rats indicates that the line difference in AcH aversion is associated more with brain ALDH2 activity than with liver ALDH2 activity.

Acetaldehyde↗
PubMed2004

Comparison of deramciclane to benzodiazepine agonists in behavioural activity of mice and in alcohol drinking of alcohol-preferring rats.

Interactions between alcohol and traditional benzodiazepine anxiolytics hamper the treatment of alcoholism-related anxiety disorders. Serotonin 5-HT(2) receptor antagonists, such as deramciclane, are anxiolytic, and considering their pharmacological profile, they might benefit alcoholics with comorbid anxiety. We studied the effects of acute deramciclane (1, 3 and 10 mg/kg i.p.) on alcohol drinking of alcohol-preferring AA rats drinking 10% (vol/vol) ethanol solution in a 4-h limited-access paradigm. Thereafter, a 5-day repeated-treatment experiment was carried out, under corresponding test design, with deramciclane (3 mg/kg i.p.) as a test drug and midazolam (1 mg/kg i.p.) as a benzodiazepine reference compound. Deramciclane had no effect on alcohol consumption in either acute or repeated dosing study. Midazolam increased ethanol drinking, as expected, when administered on successive days. A modified functional observational battery (FOB) procedure was applied to study neurological, behavioural and autonomic effects induced by deramciclane (1-30 mg/kg po) and diazepam (1-30 mg/kg po) in mice at 30 min, 2 h and 4 h after dosing. Deramciclane had a mild dopamine D(2) receptor antagonism-like effect at the highest dose. The effects of diazepam were predictable, myorelaxation-induced motor impairment and anxiolysis-related hyperlocomotion in a novel environment being the characteristic features at the two highest doses. Deramciclane appears to be a safe and well-tolerated drug and we suggest that it might be useful in the treatment of anxiety in alcoholics.

Alcohol Drinking↗
PubMed1986

Liver cytosolic aldehyde dehydrogenases from "alcohol-drinking" and "alcohol-avoiding" mouse strains: purification and molecular properties.

Liver cytosolic aldehyde dehydrogenases (AHD-2) have been isolated in a highly purified state from "alcohol-drinking" (C57BL/6J) and "alcohol-avoiding" (DBA/2J) strains of mice. The purified enzymes were resolved into three major and one minor form of activity by isoelectric focusing (IEF) techniques and showed similar zymogram patterns. The enzymes had identical subunit sizes on SDS-polyacrylamide gels: 53,000. Gel exclusion chromatography, using Ultrogel AcA34, indicated that the enzymes were dimers. The enzymes exhibited biphasic kinetic characteristics and were readily distinguished from each other. The purified forms of AHD-2 from C57BL/6J and DBA/2J mice exhibited two apparent Km values in each case: 10 microM/100 microM and 30 microM/330 microM respectively. AHD-2 exhibited a broad pH optimum in the range 7.0-9.0 and was very sensitive towards disulphuram inhibition, with 50% inhibition occurring at 0.17 microM. The kinetic results support proposals that AHD-2 may be the primary enzyme for oxidizing acetaldehyde during ethanol oxidation in vivo.

Alcohol Drinking↗
PubMed2003

[Swedish women have developed more risky and more harmful alcohol drinking habits. A survey of alcohol drinking changes among Swedes between 1997-2001].

A random sample of 1,250 persons from the general Swedish population responded to the Alcohol Use Disorders Identification Test, AUDIT. The results (72.5% response rate) were compared to the results from an identical survey made 1997 (79.8% response rate). The factor structure and the internal reliability showed good correspondence with those of 1997, indicating a stable and satisfactory psychometric quality of the Swedish AUDIT version. The female prevalence of hazardous or harmful alcohol use had increased from 11 to 15 percent between 1997 and 2001. Thus, women, particularly 28-38 years old, reported drinking more often and in greater amounts. Furthermore, the prevalence of female teetotallers had decreased from 18 to 13 percent. The corresponding trends among men were not significant but might have been underestimated due to a greater dropout, particularly among young men in the year of 2001.

Adolescent↗
PubMed1981

Dissonance and alcohol: drinking your troubles away.

Based on recent evidence supporting the assumption that cognitive dissonance is experienced as an unpleasant emotional state, and further evidence pertaining to the effects of drinking alcohol, it was predicted that among social drinkers, dissonance arousal would increase the amount of drinking and that drinking, in turn, would reduce dissonance and subsequent attitude change. This hypothesis was tested in the first two experiments by having subjects taste rate different brands of an alcoholic beverage--ostensibly to test taste discrimination but in fact to measure the amount of drinking--immediately after dissonance was aroused by having them write a counterattitudinal essay. The effect of drinking on dissonance reduction was assessed by measuring subjects' postattitudes immediately after the drinking task. Both experiments found that although dissonance arousal had little effect on the amount of drinking, whatever drinking occurred was sufficient to eliminate dissonance-reducing attitude change. The second experiment further established that these results occurred for light as well as heavy social drinkers. Evidence that the dissonance-reducing effect of drinking resulted form some effect of drinking alcohol was provided by the finding, in the second and third experiments, that neither water or coffee drinking was sufficient to eliminate attitude change in this paradigm. Both the practical and theoretical implications are discussed. The practical implication is that some forms of alcohol abuse may evolve through the reinforcement of drinking as a means of reducing dissonance; the theoretical implication is that dissonance may be frequently reduced through behaviors that ameliorate the feelings of dissonance without involving cognitive change.

Adult↗
PubMed2005

Effect of the combination of naltrexone and baclofen, on acquisition of alcohol drinking behavior in alcohol-preferring rats.

Recent surveys suggest that positive outcomes in the pharmacotherapy of alcoholism may be obtained through drug combinations. The present study evaluated the effect of the combination of the opioid receptor antagonist, naltrexone, with the GABA(B) receptor agonist, baclofen, on the acquisition of alcohol drinking behavior in Sardinian alcohol-preferring (sP) rats. Rats were treated with either saline, 0.5 mg/kg naltrexone, 1mg/kg baclofen, or 0.5 mg/kg naltrexone plus 1mg/kg baclofen once a day for 10 days. Alcohol was offered immediately after the first drug injection under the 2-bottle regimen. Alcohol intake in saline-treated rats rose to 5-6 g/kg/day within a few days, indicative of a rapid acquisition of alcohol drinking behavior. Neither naltrexone nor baclofen, when given alone, affected alcohol drinking behavior. In contrast, the drug combination resulted in a significant reduction in daily alcohol intake and retardation in the acquisition of alcohol drinking behavior. These results suggest that combination of naltrexone plus baclofen may result in a synergistic reduction in alcohol intake in sP rats. These results are discussed in terms of naltrexone and baclofen exerting a concomitant and reciprocally potentiating inhibitory action on alcohol-induced activation of mesolimbic dopamine transmission.

Alcohol Drinking↗
PubMed2000

Accumulation of hemoglobin-associated acetaldehyde with habitual alcohol drinking in the atypical ALDH2 genotype.

BACKGROUND: Those with the atypical genotypes of low Km aldehyde dehydrogenase (ALDH2) have high blood concentrations of free acetaldehyde, an active metabolite of ethanol, after drinking alcohol. In the present study, we measured acetaldehyde reversibly bound to hemoglobin (HbAA) in Japanese male workers. METHODS: One hundred and sixty Japanese male workers in one plant participated with informed consent. The subjects were genotyped for the ALDH2 polymorphism by polymerase chain reaction method. HbAA levels were measured using a high performance liquid chromatography system with a fluorescence detector. For the study in which we examined accumulation of HbAA, eight Asian male volunteers participated with informed consent. RESULTS: Although HbAA levels were significantly correlated with recent alcohol consumption in both typical (ALDH2*1/*1) and atypical (ALDH2*1/*2) genotypes, the slope in ALDH2*1/*2 was significantly steeper than that in ALDH2*1/*1. Multiple regression analysis on relevant factors for HbAA revealed that not only recent but also daily alcohol consumption increased HbAA levels in those with the ALDH2*1/*2 genotype, which suggests that HbAA accumulates with habitual drinking. We measured HbAA levels before, during, and after alcohol consumption--one drink (0.4 ml/kg) per day--for 7 consecutive days in male volunteers. During the drinking period, HbAA linearly increased in ALDH2*1/*2 (n = 4) but not in ALDH2*1/*1 (n = 4). After reaching peak levels (+76.1 nmol/g hemoglobin) following the seventh drink, HbAA levels gradually decreased but were significantly higher for 3 days after drinking was discontinued. CONCLUSIONS: We demonstrated that HbAA levels accumulate with habitual alcohol drinking in the atypical ALDH2 genotype. HbAA was shown to be a good biomarker for increased internal exposure levels to acetaldehyde.

Acetaldehyde↗
PubMed1999

[A sex life and the use of alcoholic drinks].

Illicit sexual relationship and drinking of alcoholic drinks were brought into statistically significant "competitive" relationship in a testing examination of 957 men and women on the basis of the system analysis of the secured findings, which fact has a peculiar effect on both the age of the start of sexual life and the first occurrence of being infected with a venereal disease. Established in the above examination was also the character of correlation between the rate and ways for formation of types of drinking alcoholic drinks and level of education, age, and social status.

Adolescent↗
PubMed2005

Possible interactions of the endothelial constitutive nitric oxide synthase genotype with alcohol drinking and walking time for high serum uric acid levels among Japanese.

A variable number of tandem repeat polymorphism located in intron 4 of the gene for endothelial constitutive nitric oxide synthase (ecNOS) is reported to be significantly associated with the nitric oxide level, which influences serum uric acid (SUA). To cast light on any association between the polymorphism and hyperuricemia, as well as gene-environment interactions, a cross-sectional study was conducted for 703 health checkup examinees (213 men and 490 women). The age-adjusted odds ratio (aOR) of hyperuricemia (> or =7 mg/dL) for ecNOS 4/4, 4/5, or 5/6 genotypes (non-5/5 group) as compared with the 5/5 genotype was 2.41 (95% confidence interval [CI], 1.09-5.30) in men. The aORs for drinking alcohol relative to never drinking were found to be 8.93 (95% CI, 1.02-78.16) among men with non-5/5 genotypes and 1.76 (95% CI, 0.59-5.26) for their 5/5 counterparts. Moreover, the aORs for heavy drinking (> or =50 mL/d) were 23.16 (95% CI, 2.14-250.35) and 2.48 (95% CI, 0.75-8.15), respectively. The interaction between the genotype and current drinking was 3.10 (95% CI, 0.45-21.41). The aORs for more than 30 minutes of daily walking relative to 30 minutes or less of daily walking were found to be 1.54 (95% CI, 0.40-5.95) among men with non-5/5 genotypes and 0.31 (95% CI, 0.12-0.81) for their 5/5 counterparts. The interaction between the genotype and more than 30 minutes of daily walking was 4.92 (95% CI, 0.95-25.64). This study indicated that the ecNOS variable number of tandem repeat polymorphism influences the SUA level in men. Although the interactions were not significant, alcohol intake may be more influential among men with non-5/5 genotypes and walking may be more effective among men with the 5/5 genotype. These findings would be informative for men with high SUA levels.

Adult↗
PubMed1987

Renal artery stenosis: an example of how the periphery can modulate voluntary alcohol drinking.

Voluntary alcohol drinking, using a free-access procedure, was studied in rats three weeks after unilateral renal artery stenosis was produced by applying a 0.20 mm solid silver clip to the left renal artery (Two-Kidney, One-Clip, Hypertension). The group of animals with the arterial clip drank significantly less alcohol and more water than a sham-operated group. The two groups, however, drank similar amounts of a palatable glucose solution, suggesting that they did not differ in taste sensitivity. Blood alcohol levels measured for six hours following a 2.5 g/kg intraperitoneal injection of alcohol indicated that the difference in alcohol consumption between the two groups could not be accounted for in terms of differences in drug disposition or metabolism. These findings provide an example of a previously unknown type of control which originates in the periphery and contributes to the regulation of voluntary alcohol drinking.

Alcohol Drinking↗
PubMed2001

[Is drinking alcohol good for your health?].

Numerous epidemiological studies have disclosed documented evidence that light to moderate consumption of any alcoholic beverage is associated with approximately 20% reduction in cardiovascular disease risk. This finding applies to both men and women and to healthy individuals as well as those with coronary heart disease, diabetes, hypertension, or heart failure. Nevertheless, the issue of including a recommendation for mild to moderate alcohol consumption within the routine recommendations for primary and secondary prevention of coronary heart disease is still controversial. The controversy is derived partly from methodological issues and partly from documented adverse health effects of excessive alcohol drinking. The key issue is the definition of the optimal dose of alcohol which guarantees a positive benefit-risk ratio, i.e. enjoying the benefits of alcohol without substantial risk. The accumulating scientific evidence shows that a daily consumption of less than 30 grams of alcohol for men and less than 15 grams for women is compatible with the above goal and is not associated with health risks. Therefore, for most individuals it is appropriate to recommend mild to moderate alcohol consumption as part of a healthy life style for the prevention of cardiovascular disease. Recommendations should be given on an individual basis, taking into account the patient's age, gender, physical and mental health status, personality and past drinking habits. The desirable quantity and its upper limit as well as drinking patterns should be clearly defined. All persons should be warned to avoid heavy drinking. Awareness of indications for abstinence from alcohol such as pregnancy, sport activity and the use of certain medications is highly important.

Alcohol Drinking↗
PubMed1988

Alcohol drinking.

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Alcohol Drinking↗
PubMed1996

Performance in the cross-maze and slip funnel tests of four pairs of rat lines selectively bred for divergent alcohol drinking behavior.

Alcohol naive rats from lines genetically selected for high and low alcohol drinking and founded on either Wistar (P/NP lines) and distinct heterogeneous stocks (AA/ANA and replicate HAD/LAD lines) were tested in the explorative cross-maze and the inescapable slip funnel. Rats of the low alcohol-consuming ANA, NP, LAD1 and LAD2 lines all exhibited a shorter latency before initiating exploration of the maze than did their high alcohol-consuming counterparts (66, 51, 33 and 51% of the values for AA, P, HAD1 and HAD2 lines, respectively). Significant line differences were also found with the slip funnel test (AA > ANA for time in a sprawling posture; P > NP but HAD1 < LAD1 and HAD2 < LAD2 for time escaping), but the directions of line differences were not consistently related to those in alcohol drinking.

Journal Article↗
PubMedDate not supplied

The GABA(B) receptor agonists baclofen and CGP 44532 prevent acquisition of alcohol drinking behaviour in alcohol-preferring rats.

AIMS: The present study investigated the effect of the gamma-aminobutyric acid (GABA)(B) receptor agonists, baclofen and CGP 44532, on the acquisition of alcohol drinking behaviour in selectively bred Sardinian alcohol-preferring (sP) rats. METHODS: Baclofen [0, 1 and 3 mg/kg, intraperitoneally (i.p.)] and CGP 44532 (0, 0.1, 0.3 and 1 mg/kg, i.p.) were administered immediately before alcohol presentation to alcohol-naive sP rats. Alcohol was offered under the two-bottle free-choice regimen with unlimited access for 24 h/day. Drug treatment was repeated once daily for 10 consecutive days. RESULTS: Baclofen and CGP 44532, dose-dependently and with comparable efficacy, suppressed alcohol intake; compensatory increases in water intake left total fluid intakes virtually unchanged. CONCLUSIONS: These results demonstrate that baclofen and CGP 44532 prevent the acquisition of alcohol drinking behaviour in sP rats, and suggest the involvement of the GABA(B) receptor in the mechanisms underlying the disclosure and experience of the reinforcing properties of alcohol in this rat line.

Alcohol Drinking↗
PubMed2000

[Alcohol drinking habits assessed by the AUDIT test. Reduced maximum levels doubled the number of women with dangerous alcohol drinking].

The Alcohol Use Disorders Identification Test (AUDIT) was completed by 997 persons randomly sampled from the general Swedish population (80 percent response rate). Eighteen percent of the men and 5 percent of the women had hazardous or harmful alcohol use according to the 8+ score criterion. Since women are more sensitive to alcohol than men, a cut-off score of 6+ was suggested for them. The female prevalence of hazardous or harmful alcohol use then increased to nearly 11 percent. Hazardous or harmful alcohol use decreased with increasing age in both genders. The "binge drinking" question explained half of the total AUDIT variance and is thus the best predictor of heavy drinking in the test. The internal and test-retest reliability of the AUDIT was satisfactory. Reference values for different ages and genders are presented.

Adolescent↗
PubMed2004

Association of age at first drink with current alcohol drinking variables in a national general population sample.

BACKGROUND: Age at first drink has been found to be associated with alcohol problems in adulthood, but little is known regarding the relationship of age at first drink and current alcohol intake variables. This study was designed to determine the relationship of age at first drink to traditional drinking variables as well as novel current drinking variables assessed for the first time in a national general population sample. METHOD: Data on age of first drink, pathological drinking (DSM-IV alcohol abuse or dependence) and alcohol intake on typical drinking occasions were collected on a national general population sample of 2631 subjects by means of computerized telephone interviewing. Variables assessed for the first time in a national survey included the duration of the typical drinking episode and the predicted peak blood alcohol levels achieved during those episodes. RESULTS: Data from 2276 subjects who reported an age at first drink were used in this study. Men and lifetime pathological drinkers reported an earlier age at first drink than did, respectively, women or lifetime nonpathological drinkers. There were significant regression coefficients between age at first drink and several current drinking measures. The largest coefficients were usually found within younger age groups. CONCLUSIONS: Age at first drink may be a useful predictive variable for some current drinking measures, including predicted peak blood alcohol levels as well as lifetime alcohol pathology. Further support was provided for the "convergence" hypothesis that the drinking habits of women have become more like those of men.

Adolescent↗
PubMed1990

Labelling alcoholic drinks: percentage proof, original gravity, percentage alcohol or standard drinks?

Drivers who wish to stay 'under the limit', problem drinkers wishing to control their drinking and literally anyone who drinks alcohol and is concerned about their health are all increasingly exhorted to monitor their alcohol intake by counting 'standard drinks' (each containing 8-14 g, depending on the country in question). Unfortunately, the evidence presented in this paper suggests that this system permits many errors. In particular, it requires two assumptions to be met: (1) that drinks of the same beverage type (i.e. beer, wine, fortified wine or spirits) normally contain the same percentage of alcohol by volume; and (2) that people serve, or are served, alcoholic drinks in standard serves. It is shown that in practice the strength of drinks available for sale of a given beverage type varies widely and that 'atypical' strengths form a significant proportion of alcohol sales. Furthermore, whether drinking occurs in a private residence or on licensed premises, it is usual for quantities greater than the supposed Australian standard of 10 g to be served. In practice, most people are unaware of the strengths of different beverages or the rough equivalences between them. Even if they are taught the standard drink system, they cannot make allowances for 'atypical' variations in strength. It is suggested these problems could be readily overcome if all alcohol containers were labelled in terms of standard drinks. The benefits of such a labelling system are discussed with regard to health promotion, accident prevention and the accuracy of surveys of alcohol use.

Journal Article↗