To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.


Saturday, December 25, 2010

Alcohol research: past, present, and future

Created forty years ago, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) has played a major role in the great strides made in the understanding, treatment, prevention, and public acceptance of alcohol-use disorders

Throughout most of U.S. history “habitual drunkenness” was viewed as a problem of moral degeneracy or character flaw inherent in the individual. 

However, the wealth of scientific evidence amassed throughout NIAAA's history has established alcoholism as a medical condition, that is, as a disease for which affected individuals should feel no shame or be treated with disdain. 

We look at the developments in alcohol epidemiology, typology, etiology, prevention, and treatment research over the past 40 years. 

We also discuss how NIAAA addresses alcohol disorders from a life-course framework, affecting all stages of the lifespan, from fetus through child, adolescent, and young adult, to midlife/senior adult, with each stage involving different risks, consequences, prevention efforts, and treatment strategies.

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Tackling alcohol misuse is everyone's responsibility

Christmas is a time for celebration, yet sadly scenes of anti-social behaviour are all too common in our pubs and clubs, on our streets and beaches, and in other social settings. ''Anti-alcohol'' lobby groups apparently revel in using the silly season as a platform to wag their finger at the companies which produce these alcoholic brands.

The alcohol industry argues that to combat under-age and irresponsible drinking among young people, individuals need to take responsibility for their actions.

But for many Australians, the conversation has progressed from simply putting the onus of alcohol misuse solely on the drinker, with recognition that tackling such a problem is a shared responsibility. We know that alcohol misuse costs the Australian economy $36 billion each year. The high human and financial cost is such a concern it has been identified as a priority issue by the World Health Organisation.   > > >   Read More

Alcohol laws punish those already drinking responsibly

Another year, another silly season. Over the past few weeks we have seen the inevitable reports of people getting drunk and behaving badly. During schoolies week it was images of teenagers celebrating the end of school by drinking too much. And on the eve of the new year, we will no doubt see more reports of people drinking to excess and creating a headache for society. Inevitably, anti-alcohol groups have responded as they always do - by attacking the product rather than the behaviour.

Whether it is schoolies, Christmas or New Year, the argument is that if we limit the availability or type of alcohol, increase the tax or close the pubs early, the problems associated with alcohol misuse will surely start to vanish.

These measures penalise most Australians who drink responsibly. They ignore the obvious if rather inconvenient truth: it is not what people drink but how they drink that results in drunkenness and the associated bad outcomes, including alcohol-related violence.
As producers of alcoholic beverages, we actively encourage responsible consumption and share the concerns about alcohol misuse, but isn't it time we tackled the issue at the source? > > > >  Read More

Alcohol and Crime in Wyoming - 2009/2010

This report contains alcohol-related information collected in all twenty-three counties in Wyoming during a twelve-month time period (July 1, 2009 through June 30, 2010) by the Wyoming Association of Sheriffs and Chiefs of Police. Information was collected from a total of 18,863 persons who were arrested and subsequently detained in a county detention facility. The alcohol-related arrest data contained in this report provides a detailed, statistical picture of the impact of alcohol abuse on crime in Wyoming.
This Executive Summary highlights a few of the significant findings contained in this report. It focuses on issues that are of obvious concern or which may be of greater interest to the general public; however, a careful review of other relevant findings and statistics contained in the main body of this report is essential in order to gain a more complete perspective of the impact of alcohol on crime in Wyoming.

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Genome-wide association study of theta band event-related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence

Event-related brain oscillations (EROs) represent highly heritable neuroelectrical correlates of human perception and cognitive performance that exhibit marked deficits in patients with various psychiatric disorders. 

We report the results of the first genome-wide association study (GWAS) of an ERO endophenotype—frontal theta ERO evoked by visual oddball targets during P300 response in 1,064 unrelated individuals drawn from a study of alcohol dependence. 

Forty-two SNPs of the Illumina HumanHap 1 M microarray were selected from the theta ERO GWAS for replication in family-based samples (N = 1,095), with four markers revealing nominally significant association. 

The most significant marker from the two-stage study is rs4907240 located within ARID protein 5A gene (ARID5A) on chromosome 2q11 (unadjusted, Fisher's combined P = 3.68 × 10−6). 

However, the most intriguing association to emerge is with rs7916403 in serotonin receptor gene HTR7P = 1.53 × 10−4), implicating the serotonergic system in the neurophysiological underpinnings of theta EROs. 

Moreover, promising SNPs were tested for association with diagnoses of alcohol dependence (DSM-IV), revealing a significant relationship with the HTR7 polymorphism among GWAS case–controls (P = 0.008). 

Significant recessive genetic effects were also detected for alcohol dependence in both case–control and family-based samples (P = 0.031 and 0.042, respectively), with the HTR7 risk allele corresponding to theta ERO reductions among homozygotes. 

These results suggest a role of the serotonergic system in the biological basis of alcohol dependence and underscore the utility of analyzing brain oscillations as a powerful approach to understanding complex genetic psychiatric disorders.

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Fine Mapping Quantitative Trait Loci that Influence Alcohol Preference Behavior in the High and Low Alcohol Preferring (HAP and LAP) Mice

The High Alcohol Preferring (HAP1) and Low Alcohol Preferring (LAP1) mouse lines were selectively bred for differences in alcohol intake. 
The HAP1 and LAP1 mice are essentially non-inbred lines that originated from an outbred colony of HS/Ibg mice, a heterogeneous stock developed from intercrossing 8 inbred strains of mice. 
In a former genomewide SNP association study, we identified quantitative trait loci (QTL) on chromosomes 1, 3, 5, and 9 (Bice et al. 2009). Provisional QTL were also identified on chromosomes 8 and X. 
In the present study, using the same F2 DNA samples, we placed a much denser set of SNPs within each of those QTL regions. Using the same analytical approach employed previously, which utilizes ancestral recombination to fine map the QLT interval, we obtained significant LOD scores on chromosomes 1, 3, and 9, only. 
Our results using a dense set of SNP markers suggest that there are multiple loci contributing to alcohol preference on those three chromosomes. 
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Friday, December 24, 2010

The Epidemiology of DSM-IV Alcohol Use Disorders amongst Young Adults in the Australian Population

The aim of the study was to examine the descriptive epidemiology of 12-month alcohol use disorders (AUDs) amongst young adults in the Australian general population. 

The 2007 National Survey of Mental Health and Well Being, a nationally representative household survey of 8841 Australian adults (16–85 years), assessed participants for symptoms of the most prevalent DSM-IV mental disorders. Young adults were over-sampled to provide detailed information on this age group.
11.1% of young adults in the Australian population were diagnosed with an AUD. Compared with the rest of the young adult sample, young adults with AUDs were at greater risk of reporting another drug use disorder, an anxiety disorder, high levels of consumption, a medium or high score on the Kessler Psychological Distress Scale, and a moderate to severe score on the WHO Disability Assessment Schedule 2.0. Mental health services were rarely used by young adults with AUDs. Difficulties in differentiating young adults diagnosed with abuse and those diagnosed with dependence with the criteria we used supported accumulating evidence questioning the validity of the abuse-dependence distinction. 

AUDs in young adulthood are prevalent and associated with comorbid psychopathology, risky levels of alcohol consumption and disability. Despite the clinical significance of AUDs in this age group, few young adults with these disorders use mental health services. In this age group, the proposed changes for DSM-V regarding the classification of AUD would seem helpful. 

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Thursday, December 23, 2010

Mental and personality disorders and abstinence from alcohol: results from a national household survey

The beneficial outcomes associated with moderate compared with low alcohol intake or abstinence may be due to the inclusion of people as ‘low consumers’, who have stopped consumption because of poor health. 

We investigated the association between alcohol abstinence and symptoms of common mental disorder and personality disorder, distinguishing between lifelong abstinence and abstinence following previous consumption.

Analyses were based on the British National Survey of Psychiatric Morbidity 2000, which sampled 8580 residents aged 16–74 years. Hazardous drinking (Alcohol Use Disorders Identification Test) was excluded. Symptoms of common mental disorder (depression/anxiety) were identified by the Clinical Interview Schedule. The screening questionnaire of the Structured Clinical Interview for Axis II Personality Disorders was used to identify potential personality disorder. Self-reported alcohol abstinence was divided into lifelong abstinence and previous consumption. Previous consumers were asked why they had stopped. Covariates included socio-economic status, social activity and general health status.

After adjustment, alcohol abstinence was associated with both common mental disorder symptoms and any personality disorder, but only for previous consumers, in whom odds ratios were 1.69 (95% CI 1.23–2.32) and 1.45 (95% CI 1.09–1.94). Associations were non-specific, being apparent for most individual mental disorder symptoms and personality disorder categories. More detailed analysis indicated that associations were again limited to previous consumers who reported ceasing alcohol consumption for health reasons.
Worse mental health in low alcohol consumers, particularly those who have previously ceased for health reasons, should be taken into account when interpreting associations between moderate (compared with low) alcohol consumption and beneficial health outcomes.

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Repeated exposure to moderate doses of ethanol augments hippocampal glutamate neurotransmission by increasing release

The present study used conventional and quantitative microdialysis to assess glutamatergic and GABAergic neurotransmission in the hippocampal CA3 area of the rat following a moderate-dose ethanol treatment regimen. 

Male Wistar rats received 3.4 g/kg of ethanol or water for 6 days via gastric gavage. Microdialysis experiments commenced 2 days later. Basal and depolarization-induced glutamate overflow were significantly elevated in ethanol-treated animals. Basal and depolarization-induced gamma-aminobutyric acid (GABA) overflow were unaltered. Quantitative no-net-flux microdialysis was used to determine if changes in dialysate glutamate levels following ethanol administration are due to an increase in release or a decrease in uptake. To confirm the validity of this method for quantifying basal glutamate dynamics, extracellular concentrations of glutamate and the extraction fraction, which reflects changes in analyte clearance, were quantified in response to retro-dialysis of the glutamate uptake blocker trans-pyrrolidine-2,4-dicarboxylic acid (tPDC). tPDC significantly decreased the extraction fraction for glutamate, resulting in augmented extracellular glutamate concentrations. 

Repeated ethanol administration did not alter the glutamate extraction fraction. However, extracellular glutamate concentrations were significantly elevated, indicating that glutamate release is increased as a consequence of repeated ethanol administration. 

These data demonstrate that repeated bouts of moderate ethanol consumption alter basal glutamate dynamics in the CA3 region of the dorsal hippocampus. Basal glutamate release is augmented, whereas glutamate uptake is unchanged. 

Furthermore, they suggest that dysregulation of glutamate transmission in this region may contribute to the previously documented deficits in cognitive function associated with moderate dose ethanol use.

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Alcohol Seeking and Consumption in the NVHL Neurodevelopmental Rat Model of Schizophrenia

Alcohol abuse in schizophrenia exceeds rates in the general population and worsens illness outcomes. Neonatal ventral hippocampal lesion (NVHL) rats model multiple schizophrenia dimensions including addiction vulnerability. 

This study compared NVHL vs. SHAM-controls in operant alcohol seeking and consumption. 

NVHLs enhanced consumption of combined ethanol/sucrose solution but neither ethanol or sucrose only solutions, consistent with increased vulnerability specific to carbohydrate-laden alcohol beverages typically consumed in early stages of human alcoholism.

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Alcohol-related discussions in health care – a population view

The present study aimed to evaluate the frequency and the target group of alcohol screening and brief interventions in health care settings and how well this level of activity reflects public opinion.
A random sample of Finns aged 15–69 with a 74% response rate (n=2725).
Frequency counts were used to evaluate the level of activity. Logistic regression models were used to examine which groups were asked and advised about alcohol use and which groups considered it useful.
Over 90% had positive attitudes towards being asked about their alcohol use. Of those who had been in contact with health care (n=2062) in the 12 months before the survey, 33% had been asked about their alcohol use, being most often men, young, heavy drinkers and those of high socioeconomic status. 37% of those who had been asked were given advice, being most often heavy drinkers and those with a normal body mass index. However, 50% of heavy drinkers who had been asked about their alcohol use had not been advised about it. 72% of those who had been advised considered it useful, especially older subjects, and including also heavy episodic drinkers, though less than others.
In Finland, the frequency of health care professionals asking and giving advice on alcohol is relatively low. However, public opinion towards these discussions is positive. Our results encourage the support and uptake of systematic screenings and brief interventions in health care settings.

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TPH2 polymorphisms and alcohol-related suicide

Substantial evidence from family, twin, and adoption studies corroborates implication of genetic and environmental factors, as well as their interactions, on suicidal behavior and alcoholism risk. 

Serotonergic disfunction seems to be involved in the pathophysiology of substance abuse, and has also an important role in suicidal behavior. Recent studies of the tryptophan hydroxylase 2 showed mild or no association with suicide and alcohol-related suicide. 

We performed SNP and alcohol analysis on 388 suicide victims and 227 controls. 

The results showed association between suicide (P(χ2) = 0.043) and alcohol-related suicide (P(χ2) = 0.021) for SNP Rs1843809. A tendency for association was determined also for polymorphism Rs1386493 (P(χ2) = 0.055) and alcohol-related suicide. Data acquired from psychological autopsies in a subsample of suicide victims (n = 79) determined more impulsive behavior (P(χ2) = 0.016) and verbal aggressive behavior (P(χ2) = 0.025) in the subgroup with alcohol misuse or dependency.

In conclusion, our results suggest implication of polymorphisms in suicide and alcohol-related suicide, but further studies are needed to clarify the interplay among serotonergic system disfunction, suicide, alcohol dependence, impulsivity and the role of TPH2 enzyme.

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Acamprosate reduces ethanol drinking behaviors and alters the metabolite profile in mice lacking ENT1

Acamprosate is clinically used to treat alcoholism. However, the precise molecular functionality of acamprosate in the central nervous system remains unclear, although it is known to antagonize glutamate action in the brain. 

Since elevated glutamate signaling, especially in the nucleus accumbens (NAc), is implicated in several aspects of alcoholism, we utilized mice lacking type 1 equilibrative nucleoside transporter (ENT1), which exhibit increased glutamate levels in the NAc as well as increased ethanol drinking behaviors. 

We found that acamprosate significantly reduced ethanol drinking of mice lacking ENT1 (ENT1–/–) while having no such effect in wild-type littermates. 

We then analyzed the basal and acamprosate-treated accumbal metabolite profiles of ENT1–/–and wild-type mice using in vivo 16.4T proton magnetic resonance spectroscopy (MRS). 

Our data show that basal glutamate + glutamine (Glx), glutamate, glutamine and N-acetylaspartatic acid (NAA) levels are increased in the nucleus accumbens (NAc) of ENT1–/–compared to wild-type mice. 

We then found that acamprosate treatment significantly reduced Glx and glutamine levels while increasing taurine levels in the NAc of only ENT1–/–compared to their saline-treated group while normalizing other metabolite compared to wild-type mice. 

This study will be useful in the understanding of the molecular basis of acamprosate in the brain.

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Wednesday, December 22, 2010

Effect of Alcohol Consumption on In Vitro Fertilization

To estimate whether alcohol use at the initiation of an in vitro fertilization (IVF) cycle is associated with IVF outcomes.

In this prospective cohort study, men and women completed a self-administered questionnaire before their first IVF cycle. 

Participants reported alcohol type, amount, and frequency consumed. Discrete survival analysis was applied to calculate the odds ratio (OR) and 95% confidence interval (CI) for live birth—the primary outcome. Secondary outcomes were cycle characteristics and points of failure in the IVF process (cycle cancellation, failed fertilization, implantation failure, and spontaneous abortion). We conducted multicycle analyses with final models adjusted for potential confounders that included cycle number, cigarette use, body mass index, and age.

A total of 2,545 couples contributed 4,729 cycles. Forty-one percent of women and 58% of men drank one to six drinks per week. Women drinking at least four drinks per week had 16% less odds of a live birth rate compared with those who drank fewer than four drinks per week (OR 0.84, CI 0.71–0.99). For couples in which both partners drank at least four drinks per week, the odds of live birth were 21% lower compared with couples in which both drank fewer than four drinks per week (OR 0.79; CI 0.66–0.96).

Consumption of as few as four alcoholic drinks per week is associated with a decrease in IVF live birth rate.

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Association between the 5-HTR1B gene polymorphisms and alcohol dependence in a Han Chinese population

The human serotonin receptor 1B (HRT1B) plays an important role in regulating serotonin release. 

Previous research has suggested that the genetic variation of the HTR1B gene may confer susceptibility to alcoholism or some subtypes of alcohol dependence, but the evidence has been inconsistent.

The aim of the present study is to examine whether polymorphic variants of the HTR1B gene are associated with alcohol dependence subtypes or drinking-related behaviors in Chinese Han population. 

Alcohol-dependent (AD) male patients (n = 135) and controls (n = 143) were genotyped for two polymorphisms: A161T in the promoter region and the synonymous variation G861C in the coding region of HTR1B. 

The results showed that the A161T polymorphism was associated with alcohol dependence (T vs A allele: p = 0.002; OR = 2.18, 95% CI:1.32–3.60). This association was strengthened in those with positive family history (OR = 3.12, 95% CI: 1.71-5.70) and/or early-onset (OR = 4.53, 95% CI: 2.18-9.44) of alcohol dependence. The A161T variant was also significantly associated with age of onset of alcoholism (p = 0.001). 

Furthermore, there was a significant difference of haplotypic frequencies between patients and controls (X2 = 14.84, df = 3, p = 0.002), with one common haplotype AG of being significantly underrepresented among the patient group compared to the control group (34% vs. 47.7%, permutation p = 0.0034; OR = 0.56; 95% CI: 0.39-0.79). 

These findings confirm HTR1B as a susceptibility gene for alcohol dependence in the sample of Chinese Han population. 

The HTR1B A-161 T polymorphism may be particularly valuable as a functional genetic marker for alcoholism and merits additional study.

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Association of CHRM2 polymorphisms with severity of alcohol dependence

The cholinergic muscarinic 2 receptor gene (CHRM2) has been considered a candidate gene for the alcohol dependence in that it might underpin certain risk factors for this condition. 

This study examined variations in the CHRM2 between the patients with alcohol dependence and population controls in Korean and explored the associations between CHRM2CHRM2 were genotyped using the TaqMan assay and analyzed with the severity of symptoms of alcohol dependence. 

We found that although SNP rs324650 showed marginal association with the risk of alcohol dependence (P = 0.03), the significance of the result was not sustained after multiple corrections. 

SNP rs1824024 was significantly associated with the AUDIT and ADS scores in patients (P = 0.005 and 0.003, respectively). 

These findings suggested that the muscarinic acetylcholine function might be related not alcohol dependence itself but the severity of alcohol dependence in Korean population.

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NIH-led study identifies genetic variant that can lead to severe impulsivity

A multinational research team led by scientists at the National Institutes of Health has found that a genetic variant of a brain receptor molecule may contribute to violently impulsive behavior when people who carry it are under the influence of alcohol.  A report of the findings, which include human genetic analyses and gene knockout studies in animals, appears in the Dec. 23 issue of Nature.

“Impulsivity, or action without foresight, is a factor in many pathological behaviors including suicide, aggression, and addiction,” explains senior author David Goldman, M.D., chief of the Laboratory of Neurogenetics at the NIH’s National Institute on Alcohol Abuse and Alcoholism (NIAAA).  “But it is also a trait that can be of value if a quick decision must be made or in situations where risk-taking is favored.”

In collaboration with researchers in Finland and France, Dr. Goldman and colleagues studied a sample of violent criminal offenders in Finland.  The hallmark of the violent crimes committed by individuals in the study sample was that they were spontaneous and purposeless.  > > > >  Read 

A population-specific HTR2B stop codon predisposes to severe impulsivity

Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. 

The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. 

Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. 

A stop codon in HTR2B was identified that is common (minor allele frequency >1%) but exclusive to Finnish people. 

Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. 

Knockout of Htr2b increased impulsive behaviours in mice, indicative of predictive validity. 

Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioural phenotypes using founder populations, and indicates a role for HTR2B in impulsivity.

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Early Adolescence as a Critical Window During Which Social Stress Distinctly Alters Behavior and Brain Norepinephrine Activity

Many neural programs that shape behavior become established during adolescence. Adverse events at this age can have enduring consequences for both adolescent and adult mental health. 

Here we show that repeated social stress at different stages of adolescent development differentially affects rat behavior and neuronal activity. 

Early-adolescent (PND 28, EA), mid-adolescent (PND 42, MA), and adult (PND 63) rats were subjected to resident-intruder social stress (7 days) and behavior was examined 24–72h later. 

In EA rats selectively, resident-intruder stress increased proactive responses in the defensive burying and forced swim tests. 

In adult rats, resident-intruder stress decreased burying behavior regardless of whether the animal was stressed as an adult or during early adolescence. 

As the locus coeruleus (LC)–norepinephrine system has been implicated in proactive defense behaviors, LC neuronal activity was quantified in separate cohorts. 

Stressed EA rats had elevated spontaneous LC discharge rates and diminished responses to sensory stimuli compared with controls. 

Microinjection of a CRF antagonist into the LC selectively inhibited neurons of stressed EA rats, suggesting that EA social stress induces tonic CRF release onto LC neurons, shifting the mode of discharge to an activated state that promotes active defensive behaviors. 

In all adult groups, resident-intruder stress resulted in an increased phasic response to sensory stimuli with no change in spontaneous rates. 

MA was a transition period during which social stress did not affect behavior or LC activity. 

The results suggest that social stress interacts with the brain norepinephrine system to regulate defensive strategies in an age-dependent manner.

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Modulation of lipid peroxidation and antioxidant defense systems in rat intestine by subchronic fluoride and ethanol administration

Excessive consumption of fluoride and ethanol has been identified as injurious to human health. Fluoride and ethanol co-exposures are commonly seen among the alcoholics residing in endemic fluoride areas worldwide. 

This study was undertaken to examine the modulation of lipid peroxidation and antioxidant defense systems in rat intestine by subchronic fluoride and ethanol administration. 

Female Sprague-Dawley rats were divided into four groups: group I (control), group II (fluoride was given orally at a dose of 25mg/kg body weight), group III (30% ethanol was given orally at a dose of 1mL/kg body weight), and group IV (a combination of fluoride and ethanol was administered orally at the dose described for groups II and III). 

Lipid peroxidation was elevated (P<.05) in intestine of rats by fluoride or ethanol treatments for 20 or 40 days. However, glutathione content was reduced by fluoride (32 and 44%) and ethanol (21 and 40%) treatments after 20 and 40 days, respectively. 

Fluoride-exposed animals showed reduction (P<.05) in the activities of superoxide dismutase (22 and 42%), catalase (30 and 37%), glutathione peroxidase (22 and 35%), glutathione reductase (32 and 34%), and glutathione-S-transferase (24 and 30%) after 20 and 40 days.

A similar decrease (P<.05) in the activities of these enzymes was also noticed in animals exposed to ethanol for 20 or 40 days. 

The observed changes in lipid peroxidation, reduced glutathione levels, and enzyme systems were further augmented in intestine of rats exposed to fluoride and ethanol together. Intestinal histology showed large reactive lymphoid follicles along with mild excess of lymphocytes in lamina propria of villi, villous edema, focal ileitis, and necrosis of villi in animals exposed to fluoride and ethanol for 40 days. 

These findings suggest that fluoride and ethanol exposure induces considerable changes in lipid peroxidation, antioxidant defense, and morphology of rat intestine, which may affect its functions.

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Impaired perceptual judgment at low blood alcohol concentrations

Males and females show different patterns of cognitive impairment when blood alcohol concentrations (BACs) are high. 

To investigate whether gender differences persist at low BACs, cognitive impairment was tested in 21 participants (11 female, 10 male) using a brief computerized perceptual judgment task that provides error rate and response time data. Participants consumed a measured dose of alcohol (average peak BAC: females: 0.052g/100mL, males: 0.055g/100mL), and were tested at four time points spanning both the rising and falling limbs of the BAC curve, in addition to a prealcohol time point. 

Comparisons were made against performance of these same participants at equivalent time points in an alcohol-free control condition. 

Males and females displayed a trend toward slower responses and more errors, even when mildly intoxicated. 

These data indicate that cognitive function can be impaired at BACs that are below the legal limit for driving in most countries.

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Adult anxiety-related behavior of rats following consumption during late adolescence of alcohol alone and in combination with caffeine

During late adolescence (postnatal days, PNDs, 45–55), male and female hooded rats were exposed to alcohol (1.14–1.33g/kg/day), caffeine (27.03–27.22mg/kg/day) or alcohol and caffeine together (1.20–1.34g/kg/day alcohol plus 23.85–26.48mg/kg/day caffeine) via their drinking water. The rats’ anxiety-related behavior was then assessed on reaching mid adulthood at PND120 in a light–dark box and an open field. 

For males only, alcohol alone led to increased entries of the light–dark box and (compared with water- or caffeine-exposed subjects) open-field rearing. 

Alcohol and caffeine combined also increased entries of the light–dark box light compartment and open-field ambulation for males only. The drug combination led to more male ambulation than for alcohol alone, and higher occupancy of the center squares of the apparatus than for males in any other group. 

Although alcohol alone had no subsequent effects on female behavior, alcohol and caffeine combined led to fewer entries of and less time spent in the light–dark box side then females in any other group. The drug combination also led to less female ambulation in the open field compared with either water- or caffeine-exposed females. 

The results were interpreted as sex-related potentiation by caffeine of alcohol’s developmental effects that resulted in lower levels of adult anxiety in male, but higher levels in females. 

The possible significance of this outcome for humans, especially females, was discussed.

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Effects of ethanol consumption on chromatin condensation and DNA integrity of epididymal spermatozoa in rat

Alcohol abuse is considered as one of the problems associated with poor semen production and sperm quality. Both acute and chronic alcohol consumption may affect spermatozoal chromatin disorders through apoptosis. 

Therefore, for the first time, this experimental study was performed to evaluate the effect of ethanol consumption on sperm parameters and chromatin integrity of spermatozoa aspirated from cauda epididymis of rats. 

Twenty adult Wistar rats were divided into ethanol consumption and control groups. Access to ethanol and water was provided ad libitum for experimental and control animals, respectively. The cauda epididymal spermatozoa were aspirated for analysis of sperm parameters and sperm chromatin integrity with aniline blue (AB), chromomycin A3 (CMA3), toluidine blue (TB), and acridine orange (AO) assays. 

Sperm progressive and nonprogressive motility of ethanol-consuming rats were significantly decreased compared with control animals (P<.05). 

In addition, the rates of AB-reacted spermatozoa were similar in both groups (P>.05). However, with regard to CMA3, AO, and TB stainings, there was a significant increase in ethanol group when compared with the controls (P<.05). 

The majority of TB+ and AO+ spermatozoa were higher than “cut-off” value in ethanol group, whereas the mean rates of CMA3+ spermatozoa was below the “cut-off” value in both groups. 

The results showed that ethanol consumption disturbs sperm motility, nuclear maturity and DNA integrity of spermatozoa in rat. 

Therefore, ethanol abuse results in the production of spermatozoa with less condensed chromatin, and this may be one possible cause of infertility following ethanol consumption.

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The alcohol-induced locomotor stimulation and accumbal dopamine release is suppressed in ghrelin knockout mice

Ghrelin, the first endogenous ligand for the type 1A growth hormone secretagogue receptor (GHS-R1A), plays a role in energy balance, feeding behavior, and reward. Previously, we showed that pharmacologic and genetic suppression of the GHS-R1A attenuates the alcohol-induced stimulation, accumbal dopamine release, and conditioned place preference as well as alcohol consumption in mice, implying that the GHS-R1A is required for alcohol reward. 

The present study further elucidates the role of ghrelin for alcohol-induced dopamine release in nucleus accumbens and locomotor stimulation by means of ghrelin knockout mice. 

We found that the ability of alcohol to increase accumbal dopamine release in wild-type mice is not observed in ghrelin knockout mice. Furthermore, alcohol induced a locomotor stimulation in the wild-type mice and ghrelin knockout mice; however, the locomotor stimulation in homozygote mice was significantly lower than in the wild-type mice. 

The present series of experiments suggest that endogenous ghrelin may be required for the ability of alcohol to activate the mesolimbic dopamine system. 

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Androgen Receptor Polyglutamine Length Does Not Influence Serum Levels of Adipocytokines in Alcoholism: A Preliminary Retrospective Analysis

In recent years, various studies were able to show a link between serum levels of appetite-regulating peptides and alcoholism. The adipocytokines, adiponectin and resistin seem to be altered during withdrawal. We recently showed that a trinucleotide polymorphism within the coding region of the androgen receptor (AR) is linked to craving in alcohol withdrawal, an effect that was mostly mediated by leptin. 

The aim of the present preliminary retrospective study was to further elucidate whether adiponectin and resistin serum levels are regulated by this AR polymorphism as well.  

We included 50 male in-patients who were admitted for detoxification treatment. Each had a diagnosis of alcohol dependence (DSM-IV).  

Our analyses revealed that adiponectin serum levels significantly decreased, whereas resistin levels slightly increased between the day of admission and Day 7. Beyond that, we were not able to demonstrate significant associations between the investigated CAG polymorphism of the AR and adiponectin, resistin or leptin-corrected adipocytokines, either on the day of admission or on Day 7. Moreover, the polymorphism did not influence the time response of adiponectin and resistin during withdrawal.  

Genetic determinants of the AR influence alcohol withdrawal. Anyway, this preliminary retrospective analysis does not support the hypothesis that the investigated AR polymorphism has a major modifying effect on adiponectin or resistin serum levels in patients with alcoholism. 

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The Stigma of Alcohol Dependence Compared with Other Mental Disorders: A Review of Population Studies

Stigma is likely to aggravate the severe medical and social consequences of alcohol dependence. We aim to explore the characteristics of the alcohol dependence stigma by comparing it with the stigma of other conditions.  

On the basis of a systematic literature search, we identified 17 representative population studies published before July 2010 that examine aspects of the stigma of alcoholism and simultaneously of other mental, medical or social conditions. Seven surveys were located in Europe, five in North America, three in New Zealand and one each in Brazil and Ethiopia, respectively. 

Compared with people suffering from other, substance-unrelated mental disorders, alcohol-dependent persons are less frequently regarded as mentally ill, are held much more responsible for their condition, provoke more social rejection and more negative emotions, and they are at particular risk for structural discrimination. Only with regard to being a danger, they are perceived to be at a similarly negative level to that of people suffering from schizophrenia. 

Alcoholism is a particularly severely stigmatized mental disorder. Cultural differences are likely, but under-researched. We discuss possible reasons for the differences between the stigma of alcoholism and of other mental diseases and the consequences for targeted anti-stigma initiatives. 

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Tuesday, December 21, 2010

European Alcohol and health Forum

Seventh plenary meeting,
Brussels, 18 November 2010