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, January 1, 2011

Alcohol Use Disorders After Bariatric Surgery.

The increased incidence of alcohol use disorders (AUD) after bariatric surgery has been proposed despite limited empirical support. 
We sought to determine the prevalence of current and lifetime AUD and other Axis I diagnoses in patients who have undergone bariatric surgery, and to test the hypothesis that greater weight loss is associated with a higher incidence of AUD following surgery.
Individuals who underwent bariatric surgery between 2004 and 2007 were recruited for inclusion in the study. The diagnosis of current and lifetime AUD and other Axis I disorders was assessed using the Structured Clinical Interview for DSM-IV.   
A total of 51 individuals were included. The prevalence of lifetime and current AUD was 35.3% and 11.8%, respectively. No associations were found between weight loss following surgery and the development of an AUD or other Axis I diagnoses. Significantly more current AUD was reported in (1) individuals with a lifetime history of AUD compared to those without a lifetime AUD (p < 0.05), and (2) individuals undergoing Roux-en-Y gastric bypass (RYGB) compared to those undergoing the laparoscopic adjustable gastric banding (LAGB) surgery (p < 0.05).
Individuals undergoing bariatric surgery were found to have a lifetime prevalence of AUD comparable to the general population. Although weight loss was not associated with the development of an AUD following surgery, individuals with a lifetime history of AUD may be at increased risk for relapsing to alcohol use after surgery. All instances of current AUD were identified in individuals undergoing RYGB as opposed to LAGB. 

Request Reprint E-Mail:

Friday, December 31, 2010

Older adults' own reasoning for their alcohol consumption

The aim of the study was to investigate what the older adults themselves consider to be the reasons for their alcohol consumption.
The data were collected with a postal questionnaire from a random sample of 2100 elderly people (≥65 years) living in the medium-sized city of Espoo, Finland. The response rate was 71.6% from the community-dwelling sample. Altogether 868 persons responded that they use alcohol. Of them, 831 gave reasons for their drinking. We defined “at-risk users” as consuming >7 drinks per week, or ≥5 drinks on a typical drinking day, or using ≥3 drinks several times per week.
Main reasons given for alcohol consumption were “having fun or celebration” (58.7%), “for social reasons” (54.2%), “using alcohol for medicinal purposes” (20.1%), and “with meals” (13.8%). 

Younger age groups reported more often than the older age groups that they use alcohol for “having fun or celebration” and “for social reasons.” 

The older age groups used more often “alcohol for medicinal purposes”. 

Men used alcohol more often than women “as pastime” or “as sauna drink”. 

Those defined as “at-risk users” reported using alcohol because of “meaningless life,” for “relieving depression,” “relieving anxiety,” and “relieving loneliness.”
Older adults have diverse alcohol consumption habits like people in other age groups. The oldest olds reported that they use alcohol for medicinal purposes. The “at-risk users” admit they use alcohol because of meaningless life, and relieving depression, anxiety, and loneliness. 

Read Full Abstract 

Request Reprint E-Mail:

A Double-Blind, Randomized Trial of Sertraline for Alcohol Dependence: Moderation by Age and 5-Hydroxytryptamine Transporter-Linked Promoter Region Genotype

Late-onset/low-vulnerability alcoholics (LOAs) appear to drink less when treated with a selective serotonin reuptake inhibitor than placebo, whereas early-onset/high-vulnerability alcoholics (EOAs) show the opposite effect. 

We conducted a 12-week, parallel-group, placebo-controlled trial of the efficacy of sertraline in alcohol dependence (AD). 

We compared the effects in LOAs versus EOAs and examined the moderating effects of a functional polymorphism in the serotonin transporter gene. Patients (N = 134, 80.6% male, 34.3% EOAs) with Diagnostic and Statistical Manual of Mental Disorders-IV AD received up to 200 mg of sertraline (n = 63) or placebo (n = 71) daily. 

We used urn randomization, and patients were genotyped for the tri-allelic 5-hydroxytryptamine transporter protein linked promoter region polymorphism. 

Planned analyses included main and interaction effects of medication group, age of onset (≤25 years vs >25 years), and genotype (L′/L′ vs S′ carriers) on drinking outcomes. 

Results showed that the moderating effect of age of onset on the response to sertraline was conditional on genotype. There were no main or interaction effects among S′ allele carriers. 

However, in L′ homozygotes, the effects of medication group varied by age of onset (P = 0.002). At the end of treatment, LOAs reported fewer drinking and heavy drinking days when treated with sertraline (P = 0.011), whereas EOAs had fewer drinking and heavy drinking days when treated with placebo (P < 0.001).

The small cell sizes and high rate of attrition, particularly for L′ homozygotes, render these findings preliminary and their replication in larger samples necessary. 

Because AD is common, particularly in medical settings, and selective serotonin reuptake inhibitors are widely prescribed by practitioners, these findings have potential public health significance and warrant further evaluation.

Request Reprint E-Mail:

Alcohol Withdrawal During Hospitalization

For a chronic drinker, sudden alcohol withdrawal because of an unexpected hospitalization can lead to escalating withdrawal symptoms and even death if unrecognized and untreated. 

Nurses need to be aware of the prevalence of alcohol abuse in the United States and consider the possibility of unplanned alcohol withdrawal in their patients. 

This article discusses the effects on the body of chronic alcohol intake, the potential symptoms of alcohol withdrawal, and ways to recognize and treat these symptoms through early assessment and consistent intervention.

Read Full Article    (PDF)

Drinking Motivations and Experiences of Unwanted Sexual Advances Among Undergraduate Students

This study examined the relationship between drinking motivations and college students’ experiences with unwanted sexual advances. 

Undergraduates, from a public university in the mid-Atlantic region, who reported recent (30 day) alcohol use ( n = 289) completed an online survey midway through the spring 2007 academic semester. 

Experiencing an unwanted sexual advance was the outcome of interest for the present study. The independent variables included sociodemographics and a three-factor (social ease, social image or reputation, emotional distress) drinking motivation measure. Prevalence estimates as well as unadjusted and adjusted odds ratios (OR) were produced. 

A strong relationship was found between having an unwanted sexual advance and recent binge drinking as well as drinking to remove emotional distress (OR = 3.40 and 2.73, respectively, for the total sample; OR = 7.27 and 2.82 for females). 

Findings suggest that experiencing an unwanted sexual advance is associated with specific drinking motivations and more likely to occur among females. 

Further research is needed to fully understand pathways and implications. 

Request Reprint E-Mail:

Low effective organizational strategies in visual memory performance of unmedicated alcoholics during early abstinence

Alcohol-dependent patients in early abstinence show an impairment of cognitive functions which can be seen in poor implementation of newly learned skills for avoiding relapse. 

Executive dysfunction may persist during abstinence in alcohol-dependent persons, thus mitigating long-term abstinence. 

This study assessed visual memory function and choice of organizational strategies in alcoholics, as these are major factors necessary to implement ongoing behavior changes which are required for maintaining abstinence.
We investigated 25 severely alcohol-dependent male patients between days 7 to 10 of abstinence, immediately after clinical withdrawal symptoms have ceased, compared to 15 healthy age, sex, and education matched controls. Pharmacological therapy had been terminated at least four half-lifes before inclusion into the study. Visual perceptual learning and organizational strategies were assessed with the Rey-Osterrieth Complex Figure Test (R-OCF).

There were no group differences in copying or recalling the figure, but time differences occurred. Alcoholics and healthy controls performed worse in recalling than in copying. But, alcoholics used less effective organizational strategies.

There was a deficit in choice of organizational strategy in newly abstinent and unmedicated alcohol-dependent patients. Due to the imperfect organizational strategies, alcoholics might need auxiliary therapeutic care to strengthen their cognitive ability.

Read Full Article    (PDF)

News Release - Prevention of bad lifestyle habits should be tackled even before 13 years, according to PhD thesis defended at University of the Basque Country

Bad eating habits, ingestion of alcohol, sedentary lifestyles - all unhealthy life habits that are already being detected in early adolescence and that are especially predominant amongst women and young people between the ages of 19 and 26. The prevention campaigns should take very much into consideration these groups at risk and even take into account those less than 13 years. These are some of the conclusions that can be drawn from the PhD thesis presented at the University of the Basque Country (UPV/EHU) by researcher Marta Arrue, with the title, Lifestyle habits and psychological factors in adolescence and youth in the Autonomous Community of the Basque Country (CAV-EAE)

Ms Arrue studied 2,018 young people from the CAV-EAE who were asked to fill in various questionnaires. With the gathered data, she collated and analysed habits of life according to sex and age (adolescents from 13 to 17; young persons from 18 to 26).   > > >   Read More

Thursday, December 30, 2010

State Admissions to Substance Abuse Treatment Services: TEDS 1998 - 2008,

This report presents data from the Treatment Episode Data Set (TEDS) by Census division and State and jurisdiction for admissions in 2008 and trend data for 1998 to 2008. 

The report provides information on the demographic and substance abuse characteristics of admissions to treatment aged 12 and older for abuse of alcohol and/or drugs in facilities that report to individual State administrative data systems.

Read Full Report   (PDF)

Daily Telephone Monitoring Compared with Retrospective Recall of Alcohol Use among Patients in Early Recovery

Most studies comparing frequent self-monitoring protocols and retrospective assessments of alcohol use find good correspondence, but have excluded participants with significant comorbidity and/or social instability, and some have included abstainers. 

We evaluated the correspondence between measures of alcohol use based on daily interactive voice response (IVR) telephone monitoring and a 28-day modification of the Form-90 (Form-28). Participants were 25 outpatients with alcohol use disorder and significant PTSD symptomatology. 

Overall correlations between the IVR and Form-28 on days drinking and total standard drink units (SDUs) were strong for the entire sample and the subsample of drinkers (n = 7). 

Day-to-day correspondence between IVR and Form-28 was modest, but much stronger for the most recent week assessed than for the prior 3 weeks. 

Finally, the drinkers reported significantly greater total SDUs and heavy drinking days on the Form-28 than via IVR. 

The results indicate a need for further refinement of IVR methodology for treatment seeking populations as well as caution when retrospectively assessing drinking over time periods longer than a week among these individuals. 

Request Reprint E-Mail:

Utilization of residential alcoholism treatment in bipolar disorder.

Despite the high prevalence rate of comorbid alcohol dependence and bipolar disorder, little is known about how many bipolar patients are actively engaged in addiction treatment or the alcohol consumption characteristics of this group. 

This retrospective study reviewed the medical records from patients with alcohol dependence admitted to residential treatment at our institution (n = 588). 

The analyses focused on alcoholism severity measures and discharge clinical diagnoses. Patients with alcoholism + bipolar disorder compromised only 5% of the total study group. 

The number of drinking years was lower for patients with alcoholism + bipolar disorder (23.1 ± 17.7) than for those with alcoholism + depression (26.8 ± 13.9) or alcoholism alone (28.1 ± 13.2). 

A trend of higher mean lifetime maximum daily drinks was observed for patients with alcoholism + bipolar disorder; this was because of the significantly higher maximum drinks for women with bipolar disorder (21.0 ± 11.5) than for women in other diagnostic groups. 

Despite high rates of comorbidity in community-based studies, this retrospective study suggests that patients with bipolar disorder are not highly represented in residential alcoholism addiction treatment. 

Future studies are encouraged to better understand utilization rates of addiction treatment among patients with bipolar disorder and to identify clinical correlates that predispose bipolar women to high-dose drinking. 

Request Reprint E-Mail: 

The Emerging Link Between Alcoholism Risk and Obesity in the United States

The prevalence of obesity has risen sharply in the United States in the past few decades. Etiologic links between obesity and substance use disorders have been hypothesized.

To determine whether familial risk of alcohol dependence predicts obesity and whether any such association became stronger between the early 1990s and early 2000s.

We conducted analyses of the repeated cross-sectional National Longitudinal Alcohol Epidemiologic Survey (1991-1992) and National Epidemiologic Survey on Alcohol and Related Conditions (2001-2002).

The noninstitutionalized US adult population in 1991-1992 and 2001-2002.

Individuals drawn from population-based, multistage, random samples (N = 39 312 and 39 625).

Obesity, defined as a body mass index (calculated from self-reported data as weight in kilograms divided by height in meters squared) of 30 or higher and predicted from family history of alcoholism and/or problem drinking.

In 2001-2002, women with a family history of alcoholism (defined as having a biological parent or sibling with a history of alcoholism or alcohol problems) had 49% higher odds of obesity than those without a family history (odds ratio, 1.48; 95% confidence interval, 1.36-1.61; P < .001), a highly significant increase (P < .001) from the odds ratio of 1.06 (95% confidence interval, 0.97-1.16) estimated for 1991-1992. 

 For men in 2001-2002, the association was significant (odds ratio, 1.26; 95% confidence interval, 1.14-1.38; P < .001) but not as strong as for women. 

The association and the secular trend for women were robust after adjustment for covariates, including sociodemographic variables, smoking status, alcohol use, alcohol or drug dependence, and major depression. Similar trends were observed for men but did not meet statistical significance criteria after adjustment for covariates.

These results provide epidemiologic support for a link between familial alcoholism risk and obesity in women and possibly in men.

This link has emerged in recent years and may result from an interaction between a changing food environment and predisposition to alcoholism and related disorders.

Read Full Abstract 

Request Reprint E-Mail: 

Reinforcing efficacy moderates the relationship between impulsivity-related traits and alcohol use.

Studies have shown that impulsivity-related traits are associated with alcohol use among college students. It is possible that individual differences in susceptibility to reinforcement from alcohol, which reflects the extent to which an individual values alcohol, moderates this relationship. 

Data were collected from 255 college students at a large, urban university who reported consuming alcohol at least once in the past 30 days. Two impulsivity-related-traits, Urgency and Sensation Seeking, were examined, as well as the reinforcing efficacy indices of Omax (maximum alcohol expenditure) and Demand Intensity (consumption when price = zero). 

Findings indicated that Omax moderated the relationship between both impulsivity-related traits and alcohol consumption, and between Urgency and alcohol-related problems. 

Demand Intensity also moderated the relationship between both impulsivity-related traits and alcohol use, but did not moderate the relationship between either trait and alcohol-related problems. 

Results from this study suggest that college students high in certain impulsivity-related traits and for whom alcohol is a highly valued reinforcer have a high risk for excessive alcohol consumption and an increased probability of experiencing negative alcohol-related problems. 

Request Reprint E-Mail: 

Liver experts' consensus: European citizens are drinking themselves to death

Europe is failing to deal with the life-threatening effects of excessive and regular alcohol consumption on its citizens' health. Severe diseases, such as liver cirrhosis, are growing at an alarming rate and are affecting people at a younger age than in the past. Since a number of current policies have not been successful in addressing health issues linked with alcohol across Europe, liver experts discussed a range of practical solutions to combat alcohol-related illness and death during a monothematic conference hosted by the European Association for the Study of the Liver (EASL) today.  > > > >  Read More

Wednesday, December 29, 2010

The Use of Protective Behavioral Strategies is Related to Reduced Risk in Heavy Drinking College Students with Poorer Mental and Physical Health

The present study examined the moderating role of health status (physical, mental, and social health) and the relationships between protective behavioral strategies utilized to reduce high-risk drinking (e.g., avoiding drinking games, setting consumption limits, or having a designated driver) and alcohol use and negative consequences in a sample of heavy drinking college students (N = 1,820). 

In this high risk sample, multiple regression analyses showed that stronger social health was related to increased drinking, while poorer physical, mental, and social health were related to increased alcohol negative consequences. 

Further, moderation effects revealed that increasing the use of protective behaviors was associated with significantly less drinking in those with stronger social health, as well as significantly lower numbers of negative consequences among participants with poorer physical and mental health. 

Implications for college counselors and medical personnel are discussed. 

Request Reprint E-Mail: 

Screening and Brief Interventions for Alcohol Use in College Health Centers: A Review

To provide a critical review of the efficacy of brief interventions for alcohol use in college health centers. 

Studies were included if (a) they examined brief intervention trials that were conducted in college- or university-based student health centers or emergency departments, and (b) they provided pre-post data to estimate change.  

Twelve studies suggested that screening and brief interventions in these settings are acceptable, feasible, and promote risk reduction.  

Findings support continued use of time-limited, single-session interventions with motivational interviewing and feedback components. 

Request Reprint E-Mail: :

Alcohol Use in Students Seeking Primary Care Treatment at University Health Services

Given the high rate of at-risk drinking in college students, the authors examined drinking behaviors and associated factors in students being seen in student health services for primary care visits from October 30, 2004, to February 15, 2007.
Analyses were based on Health Screening Survey completed by 10,234 college students seeking general medical treatment.  

Alcohol use was similar to other studies with 57% (n = 5,840) meeting the National Institute on Alcohol Abuse and Alcoholism criteria for at-risk drinking. 

Twenty-six percent of the students reported smoking at least once in the last 3 months. Risk factors for at-risk drinking included young age, white males, drinking at a fraternity/sorority house, and use of tobacco.  

These findings support the widespread implementation of alcohol screening and intervention in university health services. 

Request Reprint E-Mail:   

The effects of priming restrained versus disinhibited behaviour on alcohol-seeking in social drinkers

Deficient response inhibition (disinhibition) may play a causal role in alcohol abuse, with impaired inhibition occurring prior to, and acting as a risk factor for, subsequent alcohol problems. 

We experimentally primed either disinhibited or restrained behaviour while participants completed a Stop-Signal task, before examining the effects on alcohol-seeking behaviour.

Fifty three social drinkers completed a Stop-Signal task following instructions that either emphasised rapid responding at the expense of successful inhibition (Disinhibition group) or vice versa (Restrained group). Subsequent ad lib alcohol-seeking was measured with a bogus taste test.
As predicted, participants in the Disinhibition group consumed more beer during the taste test compared to participants in the Restrained group. Furthermore, within the Restrained group only, correlations indicated that those participants who responded more cautiously during the Stop-Signal task subsequently consumed less beer.
An experimental manipulation of response set during a response inhibition task, emphasising either restrained or disinhibited responding, has a causal influence on alcohol-seeking behaviour in social drinkers.

Request Reprint E-Mail:   

A longitudinal study of child mental health and problem behaviours at 14 years of age following unplanned pregnan


substantial minority of children are born as an unplanned pregnancy. Yet little is known about the impact of unplanned/unwanted pregnancy (UP) on long-term health outcomes for children.

This study aimed to examine the association between UP and child mental health and behavioural problems at 14 years, and whether this association is confounded or mediated by other variables. 

Data were from a study that included 4765 mothers and their children (48.4% female and 51.6% male) followed up from pregnancy to 14 years of the child's age in Brisbane, Australia. Child anxiety/depression, aggression, delinquency, attention problems, withdrawal problems, somatic complaints, social problems, problems, internalizing, externalizing and total problems were measured using the Achenbach's Youth Self Report at 14 years.

UP as reported by mothers at first antenatal visit predicted elevated levels of problem behaviours and increased substance use in children at 14 years. 

The impact of UP on child mental health and problem behaviours is partly due to the confounding effect of other variables, such as maternal socio-demographic status, mental health and substance use during pregnancy. 

Further research is needed to investigate the mechanism of association between UP and child aggression and early alcohol consumption at 14 years.

Request Reprint E-Mail: 

Alcohol consumption and later risk of hospitalization with psychiatric disorders: Prospective cohort study

The potential effects of alcohol intake upon the risk of psychiatric disorders have not often been investigated. 

The purpose of this study was to investigate, in a population sample, the association between self-reported amount of alcohol intake and the later risk of being registered in a Danish hospital with a psychiatric disorder. 

The prospective cohort study, the Copenhagen City Heart Study (n = 18,146), was used, containing three updated sets of alcohol intake and lifestyle covariates and up to 26 years follow-up. Alcohol intake was measured by self-report while psychiatric disorders were measured through registers. 

For women, the overall pattern showed that drinking above the sensible limits increased the risk of psychiatric disorders in general, especially for anxiety disorders where women drinking above the sensible drinking limits had a risk of 2.00 (confidence interval: 1.31–3.04) compared to women drinking below the sensible drinking limits. 

For men, the risk functions were slightly U-shaped; thus, a weekly low or moderate alcohol intake seemed to have a protective effect towards developing psychiatric disorders. 

The findings suggest sex differences in the association between alcohol consumption and risk of psychiatric disorders.

Request Reprint E-Mail: 

When Does Moderate Drinking Become A Problem?

Ever wonder when you reach for that third glass of wine or order that third cocktail if maybe you're pushing it? Well, you're hardly alone, particularly during the holiday season, when mountains of food and alcohol are heaped upon most social gatherings.    > > > >  Read More

The role of amygdaloid brain-derived neurotrophic factor, activity-regulated cytoskeleton-associated protein and dendritic spines in anxiety and alcoholism.

Innate anxiety appears to be a robust factor in the promotion of alcohol intake, possibly due to the anxiolytic effects of self-medication with alcohol. 

Brain-derived neurotrophic factor (BDNF) and its downstream target, activity-regulated cytoskeleton-associated (Arc) protein, play a role in the regulation of synaptic function and structure. 

In order to examine the role of the BDNF-Arc system and associated dendritic spines in the anxiolytic effects of ethanol, we investigated the effects of acute ethanol exposure on anxiety-like behaviors of alcohol-preferring (P) and -nonpreferring (NP) rats. 

We also examined changes in the expression of BDNF and Arc, and dendritic spine density (DSD), in amygdaloid brain regions of P and NP rats with or without ethanol exposure. 

It was found that in comparison with NP rats, P rats displayed innate anxiety-like behaviors, and had lower mRNA and protein levels of both BDNF and Arc, and also had lower DSD in the central amygdala (CeA) and medial amygdala (MeA), but not in the basolateral amygdala (BLA). 

Acute ethanol treatment had an anxiolytic effect in P, but not in NP rats, and was associated with an increase in mRNA and protein levels of BDNF and Arc, and in DSD in the CeA and MeA, but not BLA. 

These results suggest that innate deficits in BDNF-Arc levels, and DSD, in the CeA and MeA may be involved in the anxiety-like and excessive alcohol-drinking behaviors of P rats, as ethanol increased these amygdaloid synaptic markers and produced anxiolytic effects in P rats, but not NP rats.

Request Reprint E-Mail:  

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.

Read Full Abstract 

Request Reprint E-Mail: 

Ethanol exposure during the early first trimester equivalent impairs reflexive motor activity and heightens fearfulness in an avian model

Prenatal alcohol exposure is a leading cause of childhood neurodevelopmental disability. The adverse behavioral effects of alcohol exposure during the second and third trimester are well documented; less clear is whether early first trimester-equivalent exposures also alter behavior. 

We investigated this question using an established chick model of alcohol exposure. In ovo embryos experienced a single, acute ethanol exposure that spanned gastrulation through neuroectoderm induction and early brain patterning (19–22h incubation). At 7 days posthatch, the chicks were evaluated for reflexive motor function (wingflap extension, righting reflex), fearfulness (tonic immobility [TI]), and fear/social reinstatement (open-field behavior). Chicks exposed to a peak ethanol level of 0.23–0.28% were compared against untreated and saline-treated controls. 

Birds receiving early ethanol exposure had a normal righting reflex and a significantly reduced wingflap extension in response to a sudden descent. The ethanol-treated chicks also displayed heightened fearfulness, reflected in increased frequency of TI, and they required significantly fewer trials for its induction. 

In an open-field test, ethanol treatment did not affect latency to move, steps taken, vocalizations, defecations, or escape attempts. 

The current findings demonstrate that early ethanol exposure can increase fearfulness and impair aspects of motor function. Importantly, the observed dysfunctions resulted from an acute ethanol exposure during the period when the major brain components are induced and patterned. The equivalent period in human development is 3–4 weeks postconception. 

The current findings emphasize that ethanol exposure during the early first trimester equivalent can produce neurodevelopmental disability in the offspring.

Request Reprint E-Mail: 

The cerebellar GABAAR α6-R100Q polymorphism alters ligand binding in outbred Sprague–Dawley rats in a similar manner as in selectively bred AT and ANT rats

The alcohol-tolerant AT and alcohol-nontolerant ANT rat lines have been selectively bred for innate sensitivity to ethanol-induced motor impairment. 

The cerebellar GABAA receptor (GABAAR) α6 subunit alleles α6-100R and α6-100Q are segregated in the AT and ANT rats, respectively. This α6 polymorphism might explain various differences in pharmacological properties and density of GABAARs between the rat lines. 

In the present study, we have used nonselected outbred Sprague–Dawley rats homozygous for the α6-100RR (RR) and α6-100QQ (QQ) genotypes to show that these RR and QQ rats display similar differences between genotypes as AT and ANT rat lines. 

The genotypes differed in their affinity for [3H]Ro 15-4513 and classic benzodiazepines (BZs) to cerebellar “diazepam-insensitive” (DZ-IS) binding sites, in density of cerebellar [3H]muscimol binding and in the antagonizing effect of furosemide on GABA-induced inhibition of [3H]EBOB binding. 

The results suggest the involvement of α6-R100Q polymorphism in these line differences and in the differences previously found between AT and ANT rats. In addition, the α6-R100Q polymorphism induces striking differences in [3H]Ro 15-4513 binding kinetics to recombinant α6β3γ2s receptors and cerebellar DZ-IS sites. Association of [3H]Ro 15-4513 binding was ∼10-fold faster and dissociation was ∼3–4-fold faster in DZ-IS α6βγ2 receptors containing the α6-100Q allele, with a resulting change of ∼2.5-fold in equilibrium dissociation constant (KD). 

The results indicate that in addition to the central role of the homologous α6-100R/Q (α1-101H) residue in BZ binding and efficacy, this critical BZ binding site residue has a major impact on BZ binding kinetics.

Request Reprint E-Mail:

Monday, December 27, 2010

Exposure to ethanol during the last trimester of pregnancy alters the maturation and immunity of the fetal lung

The effects of ethanol exposure on fetal lungs remain under investigation. 

Previously, we demonstrated that lambs exposed to ethanol during gestation had impaired expression of pulmonary surfactant protein A, a crucial component of lung immunity. 

In this study, we investigated the effects of in utero exposure to ethanol on maturation and immunity of the fetal lung. 

Pregnant ewes were surgically implanted with an abomasal cannula and administered 1g ethanol/kg (n=8) or water (n=8) during the last trimester of pregnancy. Lambs were delivered prematurely or naturally. Neonatal lungs were assessed for maturation markers (hypoxia-inducible factor-1α [HIF-1α], HIF-2α, HIF-3α, vascular endothelial growth factor-A [VEGF-A], VEGFR-1, VEGFR-2, glycogen, and lung protein levels) and immunity (cytokines and chemokines). 

Preterm animals exposed to ethanol had significantly reduced VEGF-A mRNA (P=.066) and protein levels, HIF-1α (P=.055), HIF-2α (P=.019), VEGFR-1 (P=.088), and VEGFR-2 (P=.067) mRNA levels but no changes in HIF-3α mRNA. 

No significant changes occurred in full-term animals exposed to ethanol. 

Glycogen levels were significantly higher in preterm animals exposed to ethanol (P=.006) but not in full-term animals. 

Ethanol exposure was associated with significantly lower lung protein levels in preterm (P=.03) but not full-term animals. 

Preterm animals exposed to ethanol had significantly reduced TNF-α (P=.05), IL-10 (P=.03), chemokine (C-C motif) ligand 5 (CCL5) (P=.017), and monocyte chemotactic protein-1 (MCP-1) (P=.0004) mRNA. 

In full-term animals exposed to ethanol, the immune alterations were either sustained (TNF-α, P=.009; IL-10, P=.03) or returned to near baseline levels (CCL5 and MCP-1). 

The ethanol-mediated alterations in fetal lung maturation and immunity may explain the increased incidence of respiratory infections in neonates exposed to ethanol in utero.

Request Reprint E-Mail: