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PubMedDate not supplied

Neuromodulatory role of the endocannabinoid signaling system in alcoholism: an overview.

The current review evaluates the evidence that some of the pharmacological and behavioral effects of ethanol (EtOH), including EtOH-preferring behavior, may be mediated through the endocannabinoid signaling system. The recent advances in the understanding of the neurobiological basis of alcoholism suggest that the pharmacological and behavioral effects of EtOH are mediated through its action on neuronal signal transduction pathways and ligand-gated ion channels, receptor systems, and receptors that are coupled to G-proteins. The identification of a G-protein-coupled receptor, namely, the cannabinoid receptor (CB1 receptor) that was activated by Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive component of marijuana, led to the discovery of endogenous cannabinoid agonists. To date, two fatty acid derivatives identified to be arachidonylethanolamide (AEA) and 2-arachidonylglycerol (2-AG) have been isolated from both nervous and peripheral tissues. Both these compounds have been shown to mimic the pharmacological and behavioral effects of Delta(9)-THC. The involvement of the endocannabinoid signaling system in the development of tolerance to the drugs of abuse including EtOH has not been known until recently. Recent studies from our laboratory have demonstrated for the first time the down-regulation of CB1 receptor function and its signal transduction by chronic EtOH. The observed down-regulation of CB1 receptor binding and its signal transduction results from the persistent stimulation of the receptors by the endogenous CB1 receptor agonists, AEA and 2-AG, the synthesis of which has been found to be increased by chronic EtOH treatment. This enhanced formation of endocannabinoids may subsequently influence the release of neurotransmitters. It was found that the DBA/2 mice, known to avoid EtOH intake, have significantly reduced brain-CB1-receptor function consistent with other studies, where the CB1 receptor antagonist SR141716A has been shown to block voluntary EtOH intake in rodents. Similarly, activation of the CB1 receptor system promoted alcohol craving, suggesting a role for the CB1 receptor gene in excessive EtOH drinking behavior and development of alcoholism. Ongoing investigations may lead to the development of potential therapeutic strategies for the treatment of alcoholism.

Alcoholism↗

PubMed1988

Prepartum behavior of gilts in three farrowing environments.

To determine effects of the farrowing environment on prepartum behavior, five gilts were monitored continuously for 48 h prior to parturition in each of three farrowing systems: 1) an open farrowing pen (2.1 x 1.5 m); 2) a turn-around farrowing pen, which allowed the gilt to turn around (2.4 m long; 1.8 m wide at back, .6 at front) and 3) a straight farrowing crate (sow zone = .6 x 2.1 m). Videorecords were summarized as three 16-h segments (Period A = 48 to 32 h before the first piglet was delivered, B = 32 to 16 h and C = 16 to 0 h) for analysis of activity over time. In all systems, frequencies of postural changes and oral-nasal activities directed at the floor or wall increased as farrowing was approached, the highest frequencies occurring in Period C. Respective times spent standing, sitting and engaged in oral-nasal activities directed at floor or wall also increased over time. Pawing occurred almost exclusively in Period C. Lying upright (ventral posture) occupied a greater portion of lying time as the gilt's activity increased over time, whereas feeding and drinking behaviors did not change over time. The only behavior affected by the experimental environments was the frequency of 90 degree turns. Gilts in both open and turn-around pens showed an increasing turning frequency over time, and they turned more often in the open pen than in the turn-around pen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2003

Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers.

Alcoholic beverages are causally related to cancer of the oral cavity, pharynx, larynx and esophagus. Ethanol is oxidized to acetaldehyde and then to acetate by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), both of which have genetic polymorphisms. A review of case-control studies of the effects of ALDH2, ADH2 and ADH3 genotypes shows consistently positive associations between inactive heterozygous ALDH2 and the less-active ADH2 genotypes and the risk for esophageal cancer in East Asian heavy drinkers and this enzyme-related vulnerability may extend to light-to-moderate drinkers. Some studies suggest similar associations with the risk for head and neck cancer in moderate-to-heavy-drinking Japanese. An established carcinogen in experimental animals, acetaldehyde can interact with human DNA. ALDH2-associated cancer susceptibility fits into a scenario in which acetaldehyde plays a critical role in the development of human cancer. Alcohol flushing and drinking behavior may partly explain this carcinogenic effect in carriers of less-active ADH2 genotypes. Whether the ADH3 genotype influences head and neck cancer risk in Western nations is controversial. Professional and public education about risky conditions connected to the ALDH2 and ADH2 genotypes and environmental factors is important in a new strategic approach to the prevention of alcohol-related cancers in East Asians. The use of simple tests to identify inactive ALDH2 on the basis of alcohol flushing responses could benefit many people, by helping them to identify their own cancer risks. Such testing could also help clinicians diagnose esophageal cancer earlier, through the use of endoscopic screening in the high-risk population.

Alcohol Dehydrogenase↗

PubMed1987

Alcohol preference and regional brain monoamine contents of N/Nih heterogeneous stock rats.

The N/Nih heterogeneous stock rats were tested for alcohol drinking behavior. Rats that met criteria for high (greater than 5.0 g ethanol/kg body weight/day) and low (less than 0.5 g/kg/day) alcohol consumption were chosen, and the regional brain contents of monoamine neurotransmitters were determined in these animals. The primary finding was a lower content of serotonin and 5-hydroxyindoleacetic acid in the thalamus and hypothalamus of the high alcohol preferring N/Nih rats as compared with the low preferrers. The high preferrers were also found to have a lower content of dopamine and norepinephrine in the thalamus. The findings support the hypothesis that an inverse relationship exists between the density and/or metabolic functioning of regional brain serotonin systems and alcohol preference.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

An integrated approach to meta-analysis in alcohol studies.

The research design and methods utilized by the Collaborative Alcohol-Related Longitudinal Project are described. The project design addresses the critical need to develop procedures to assess the replicability of research results in alcohol studies. Key features of the research plan include: re-analysis of original data from multiple longitudinal studies of drinking behavior in the general population; centralization of all data analyses, developed and implemented by an interdisciplinary core staff; development of the research plan and interpretation of results in co-operation with original investigators of studies included in the project; and use of modeling procedures from meta-analysis to quantify the relative contribution of factors influencing the distribution of effect estimates across studies, including both methodological differences and aggregate level variables. The final section describes statistical methods for meta-analysis used by the project, including procedures for the calculation and combination of estimates of effect magnitude, categorical and continuous modeling procedures for use with effect sizes, and random effects models.

Alcohol Drinking↗

PubMed1996

DNA-damage processing in blood lymphocytes of head-and-neck-squamous-cell-carcinoma patients is dependent on tumor site.

It has been reported that an intrinsic susceptibility to cancer is related to the way an individual responds to DNA-damaging agents. The aim of this study was to evaluate whether, in addition to bleomycin-induced chromosomal instability, radiation-induced initial DNA damage and subsequent repair is associated with the development of head-and-neck squamous-cell carcinoma. In this study, 2 assays were performed to measure DNA damage in human peripheral-blood lymphocytes. One was a chromosomal aberration assay which determines sensitivity to chromatid breaks induced by bleomycin, the other an elegant immunochemical assay which measures the level of radiation-induced strand breaks as well as subsequent repair. Age, smoking and alcohol-drinking behavior did not influence the number of chromatid breaks, initial DNA damage or repair capacity. As has been found in previous studies, the mean number of chromatid breaks per cell was significantly different between patients (n = 18) and control persons (n = 19), whereas the amount of initial DNA damage was not. No correlation was found between the outcome of the 2 assays in the subject groups. In contrast to laryngeal-carcinoma patients, oral-cavity-carcinoma patients showed significantly slower repair capacity than controls. Our hypothesis is that the way DNA damage is processed by the patients determines at which site cancer develops in the head and neck area.

Adult↗

PubMed1976

A successful method for development of voluntary alcohol intoxication in mice.

Eight strains of male mice, C57BL, C3H SWM, SW, KK, KSB, KR and DBA, were fed on a standard pelletized diet and offered a choice of water or 10% sake solution (sake containing 10% alcohol). Both young (3 months of age) and old (8 months of age) groups were studied simultaneously. The degree of intoxication was measured by recording the drinking behavior on a pulse recorder, by calculating gaschromatographically the blood alcohol concentration, by taking depth electroencephalogram readings and so on. Intoxication, shown by lack of coordination such as grossly impaired gait, was observed only in the older mice of strain with a moderate natural alcohol preference such as C3H, SWM, SW, KK and KSB. In general, the intoxicated mice were over 9 months of age, tended to consume fluids regardless of the time of day or night and suffered a loss of body weight. The blood alcohol levels of them were over 4.6%. The threshold elevation of the ascending reticular activating system on electroencephalogram in a intoxicated mouse reached about 167%. The present study provides a successful method for the development of voluntary alcohol intoxication in mice.

Age Factors↗

PubMed1993

Recent developments in alcoholism:ethnicity.

Advances in alcohol and ethnicity epidemiology during the past decade include greater emphasis on intraethnic variation, factors influencing drinking behavior, and building conceptual models. Despite progress, most research continues to focus on ethnicity/race as a demographic variable and few studies investigate ethnic hypotheses. Although prevention and treatment of alcoholic disorders in ethnic groups have been dealt with extensively in the clinical and ethnographic literature, little rigorous research has been conducted. The key issue in this area involves the extent to which prevention and treatment programming needs to be ethnically responsive in order to be effective. The very little empirical literature that exists on this topic suggests that answers will not be simple and will vary according to aspects of acculturation status and ethnohistorical factors. The most important development during the past 10 years has undoubtedly been the federal regulatory encouragement of research on the major ethnic groups of the United States.

Alcohol Drinking↗

PubMed1990

Inpatient treatment of employed alcoholics: a randomized clinical trial on Hazelden-type and traditional treatment.

The first randomized clinical trial on the Hazelden-type of treatment showed that this AA-oriented treatment for alcoholism can result in significant improvement in drinking behavior as compared to a more traditional form of treatment. One hundred forty-one employed alcoholics were randomized to either Hazelden-type treatment (N = 74) or to traditional-type treatment (N = 67). The treatment groups were highly comparable. The bimonthly follow-up lasted one year. According to the COPES-questionnaire (short form), the treatment at the Hazelden-type institute was significantly more involving, supportive, encouraging to spontaneity and oriented to personal problems than at the traditional-type institute. In accordance the treatment drop-out rate was 7.9% at Hazelden-type institute and 25.9% at traditional-type institute (p less than 0.02). The participation in outpatient treatment was significantly better after the Hazelden-type treatment. The proportion of those abstinent (admitted ethanol consumption, 0 g/day; gammaglutamyl transferase, and mean cell volume were normal) was higher at Hazelden-type institute during the last (8-12 months) follow-up period (26.3% vs. 9.8%, p = 0.05). Fourteen percent of the Hazeldon-type institute patients and 1.9% of the traditional-type institute patients stayed abstinent during the whole 1-year follow-up period (p less than 0.05). The differences for the corresponding rates for controlled drinking (admitted ethanol consumption less than 40 g/day, GGT, and MCV normal) were in the same direction but did not reach statistical significance. Thus the Hazelden-type treatment obtained better results in 1-year abstinence rate than a more traditional-type treatment.

Adult↗

PubMed2003

The self-fulfilling influence of mother expectations on children's underage drinking.

This research examined whether mothers' expectations about their children's drinking behavior influenced their children's future alcohol use through self-fulfilling prophecies. It also investigated whether children's self-esteem, family social class, or the valence of mother expectations moderated this process. Analyses of longitudinal data from 505 mother-child dyads yielded results consistent with a self-fulfilling prophecy. The inaccurate portion of mother expectations predicted children's future alcohol use after accounting for relevant control variables. Moderation analyses indicated that this effect was stronger among higher self-esteem children and when mother expectations were positively valenced (i.e., when mothers underestimated their children's future alcohol use). The findings are discussed in terms of parent-child relationship quality, peer influences, self theories, and out-group stereotypes.

Adolescent↗

PubMed2004

Role of GABA(B) receptor in alcohol dependence: reducing effect of baclofen on alcohol intake and alcohol motivational properties in rats and amelioration of alcohol withdrawal syndrome and alcohol craving in human alcoholics.

The present paper describes the results of recent preclinical and clinical studies conducted in this laboratory in order to characterize the anti-alcohol properties of the GABA(B) receptor agonist, baclofen. At a preclinical level, the repeated administration of non-sedative doses of baclofen dose-dependently suppressed the acquisition and maintenance of alcohol drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats tested under the homecage, 2-bottle "alcohol vs water" choice regimen. Acute injection of baclofen completely blocked the temporary increase in voluntary alcohol intake occurring after a period of alcohol abstinence (the so-called alcohol deprivation effect, which models alcohol relapses in human alcoholics). Acute treatment with baclofen also dose-dependently suppressed extinction responding for alcohol (an index of motivation to consume alcohol) in sP rats trained to lever-press for oral alcohol self-administration. Taken together, these results suggest the involvement of the GABA(B) receptor in the neural substrate mediating alcohol intake and alcohol motivational properties in an animal model of excessive alcohol consumption. Further, acutely administered baclofen dose-dependently reduced the severity of alcohol withdrawal signs in Wistar rats made physically dependent upon alcohol. Preliminary clinical surveys suggest that the anti-alcohol properties of baclofen observed in rats may generalize to human alcoholics. Indeed, a double-blind survey demonstrated that repeated daily treatment with baclofen was associated, when compared to placebo, with a higher percentage of subjects totally abstinent from alcohol and a higher number of days of total abstinence. Treatment with baclofen also suppressed the number of daily drinks and decreased the obsessive and compulsive components of alcohol craving. Finally, a single non-sedative dose of baclofen resulted in the rapid disappearance of alcohol withdrawal symptomatology, including delirium tremens, in alcohol-dependent patients. In both clinical studies, baclofen was well tolerated with minimal side effects. These results suggest that baclofen may represent a potentially effective medication in the treatment of alcohol-dependent patients.

Alcohol Drinking↗

PubMed2003

Anti-relapse properties of IDN 5082, a standardized extract of Salvia miltiorrhiza, in alcohol-preferring rats.

Salvia miltiorrhiza extracts have been reported to suppress acquisition and maintenance of alcohol drinking behavior in Sardinian alcohol-preferring (sP) rats. The present study investigated whether IDN 5082, a standardized extract of Salvia miltiorrhiza, was capable of preventing, in sP rats, the development of the so-called alcohol deprivation effect (ADE), i.e. the transient increase in alcohol intake that occurs in laboratory animals after a period of alcohol deprivation. Interestingly, ADE has been proposed to model alcohol relapses in human alcoholics. The acute, intragastric administration of 25, 50, and 100 mg/kg IDN 5082 resulted in the complete suppression of the extra amount of alcohol consumed during the first hour of re-access to alcohol after 7 days of deprivation. These results suggest that IDN 5082 may possess anti-relapse properties.

Alcohol Drinking↗

PubMed2000

Attribution of injury to alcohol involvement in young adults seriously injured in alcohol-related motor vehicle crashes.

BACKGROUND: Approximately 40% of all traffic fatalities are associated with the use of alcohol. Hospitalization for serious injury after a motor vehicle crash related to use of alcohol may be an opportunity to change drinking behaviors in non-alcohol-dependent drinkers, thereby reducing the risk for future disability and death. OBJECTIVES: To determine the degree to which non-alcohol-dependent adults aged 18 to 45 years with alcohol-related vehicular trauma attributed their injury to use of alcohol. METHODS: During hospitalization, 132 subjects involved in alcohol-related motor vehicle crashes were interviewed. The interviews included the question, "To what extent do you believe your alcohol consumption was responsible for this injury?" Responses were measured on a 7-point scale ranging from 1 (not at all) to 7 (totally). RESULTS: In response to the question about attribution of injury to alcohol, 37.8% of subjects responded "not at all," 24.3 responded "somewhat," and 37.9% responded "mostly" or "totally." Spearman rank correlation between attribution of injury to alcohol involvement and blood alcohol content at admission was r = 0.440 (P < .001). CONCLUSIONS: More than 60% of patients injured in alcohol-related motor vehicle crashes attributed their injury partly or totally to use of alcohol. When alcohol-free, hospitalized patients with higher blood levels of alcohol on admission were more likely than those with lower levels to attribute their injury to alcohol. Hospitalization for a motor vehicle crash related to use of alcohol provides an opportunity for interventions to decrease drinking.

Accidents, Traffic↗

PubMed2000

Role of renin-angiotensin system in hypotension-evoked thirst: studies with hydralazine.

Injection of rats either with diazoxide (25 mg/kg iv), isoproterenol (0.33 mg/kg sc), or hydralazine (HDZ) (10 mg/kg ip) decreased arterial blood pressure from approximately 120 to 70-80 mmHg and stimulated renin secretion. However, diazoxide and isoproterenol treatments each stimulated water ingestion, whereas HDZ treatment did not. HDZ treatment did not reduce water intake evoked by systemic injection of hypertonic saline or 20% polyethylene glycol solution or by 24-h water deprivation, suggesting that HDZ treatment did not interfere with drinking behavior. In contrast, HDZ treatment markedly reduced water intake evoked by injection of diazoxide or isoproterenol or by intravenous infusion of renin. Furthermore, a highly significant correlation was observed when plasma ANG II levels were plotted as a function of plasma renin activity after intravenous infusion of renin and after diazoxide and isoproterenol treatments. However, values obtained after HDZ treatment alone or in combination with intravenous infusion of renin did not fall near the 99% confidence interval of the regression line, suggesting that HDZ treatment blocks ANG II production and/or promotes its clearance. Thus rats apparently do not increase water intake after HDZ treatment, because this drug interferes with the renin-angiotensin system. These results provide further evidence that arterial hypotension evokes thirst in rats predominantly by activation of the renin-angiotensin system.

Animals↗

PubMed2004

Histaminergic H1 and H2 receptors located within the ventromedial hypothalamus regulate food and water intake in rats.

The aim of the present study was to investigate the effect of the pharmacological blockade of histamine H1 and H2 receptors located within the ventromedial hypothalamus (VMH) on overnight food and water intake and on water intake elicited by two physiological stimuli: hyperosmolarity induced by an acute intragastric salt load and water deprivation. During the overnight period, the pharmacological blockade of both H1 and H2 VMH receptors significantly increased food intake and decreased water intake. In hyperosmotic rats, the blockade of H1 VMH receptors reduced water intake, while the blockade of H2 receptors in this same region yielded no significant effect. Additionally, in water-deprived rats, the blockade of both H1 and H2 receptors located within the VMH induced a significant decrease in water intake. The inhibitory effects on drinking behavior observed in this study do not seem to be a consequence of any "illness-inducing" effect provoked by the central administration of the antihistaminergic agents employed here, because an aversion test indicated that the injection of those compounds into the VMH does not induce any "illness-like" effect. In addition, the central administration of either mepyramine or cimetidine to dehydrated and hyperosmotic rats did not produce any reduction in locomotor activity measured in an open-field arena. Injections of the antihistaminergic agents used here into the regions that circumscribe the VMH produced no significant effects on water or food intake, indicating that the actions observed here may be specifically attributed to the set of histaminergic receptors situated within the VMH.

Animals↗

PubMed2003

Alcohol and domestic violence in a sample of incidents reported to the police of Zurich City.

The purpose of the study is to examine episodes of domestic violence reported to the police, focusing on the drinking behavior of the individuals involved. Over a period of 110 days, (November 1999-February 2000) a total of 53 calls to the emergency line of the police of the city of Zurich (Switzerland), related to domestic violence, were registered. Detailed data concerning the forms of violence, the persons involved, their alcohol intake, and the context of the incidents were collected in 42 cases by means of structured interviews of the officers who achieved the interventions and inquiries. Moreover, interviews by agreement of victims were performed in 12 cases, providing complementary data. Evidence of alcohol involvement was found in 40% of the investigated situations. Police officers thus believed there was a clear link between alcohol and violence in at least 26% of the 42 cases. The interviews of the victims suggest a wide range of attributions made to the role of alcohol in situations of domestic violence.

Adult↗

PubMed2004

[Drinking practice and alcohol-related problems: the national representative sample survey for Healthy Japan 21].

This article is the first survey report in Japan concerning the adult drinking behaviors and its overall alcohol-related problems based on a national representative sample. It deals with a wide range of alcohol topics such as frequency, volume, cultural aspects, social influence and its effect on individuals, both positive and negative as well as various other alcohol related problems. The report identified, for further implementation of Japan's national health program, "Healthy Japan 21", the following areas of focus; 1) 5% of males and 0.5% of females who are considered "Hard Drinker", the most prioritized target. Seemingly small portion of females, 0.5%, is far beyond the planned goal level. 2) The cultural and regional competency is highly expected for policy discussion and evaluation in order to decrease the hard drinker population by 20% off. 3) Clarify the definition of a "Hard drinker" and disseminate the information publicly for functional health monitoring activity by local governments.

Adult↗

PubMed1990

Emergence of alcohol expectancies in childhood: a possible critical period.

Previous investigations with adolescents (aged 12-19) have shown alcohol-related expectancies to develop in childhood prior to significant drinking experience and to covary directly with drinking behavior. To chart the development of alcohol expectancies in children as young as age 6, a procedure was developed to be as independent as possible of age-related variation in reading and language development. This instrument was administered to 114 elementary school children of both genders, distributed across grades 1 to 5. Psychometric analysis provided evidence of the test's reliability and validity. Evaluation of the developmental pattern produced two primary findings: (1) there was an overall trend of increasingly positive expectancies with age; and (2) strikingly, the bulk of the increase was observed in the third and fourth grades. Children's expectancies may be less differentiated than adolescent or adult expectancies. These findings suggest that the precursors for later alcohol use and abuse are formed in childhood and that prevention efforts may need to begin as early as third grade.

Age Factors↗