Resveratrol protects spatial learning in middle-aged C57BL/6 mice from effects of ethanol

Behavioural Pharmacology: POST AUTHOR CORRECTIONS, 30 June 2009

Spatial learning and memory have been shown to be especially vulnerable to aging and alcohol consumption. However, moderate consumption of wine has been linked to decreases in incidences of dementia. Resveratrol, a phytoestrogen found in wine, has been shown to have neuroprotective effects against the oxidative stress of ethanol.

In this study, middle-aged C57BL/6N female mice given a combination of resveratrol (44.2 mg/kg) and a low amount of ethanol (0.71 g/kg) each day for 6 weeks performed better on the Barnes maze task for spatial learning and memory than mice consuming only the low concentration of ethanol.

The results suggest that resveratrol may protect hippocampal-dependent spatial learning from the negative effects of ethanol. However, the resveratrol-ethanol combination did not provide any additional benefit to counter aging-related deficits.

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Request Reprint E-Mail: mpetro@nebrwesleyan.edu

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Commentary - The Legal Drinking Age and Underage Drinking in the United States

Arch Pediatr Adolesc Med. 2009;163(7):598-600.

Each year thousands of adolescents in the United States are killed, injured, or suffer other serious consequences of their own or another's underage drinking. The immense societal costs of underage drinking have made it a focus of concern among policymakers and public health officials. In 2006, the US Congress passed the Sober Truth on Preventing (STOP) Underage Drinking Act to help states and communities address this chronic problem. In 2007, The Surgeon General's Call to Action to Prevent and Reduce Underage Drinking appealed to Americans to do more to stop current underage drinkers from using alcohol and to keep other adolescents from starting.

This commentary will review the magnitude and consequences of underage drinking and discuss how increasing the minimum legal drinking age has helped to reduce and prevent the harm caused by drinking among adolescents.

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Request Reprint E-Mail: rhingson@mail.nih.gov

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Relationship Between Neighborhood Context, Family Management Practices and Alcohol Use Among Urban, Multi-ethnic, Young Adolescents

Prevention Science Published Online 21 Apr 2009

We examined relationships between alcohol-related neighborhood context, protective home and family management practices, and alcohol use among urban, racial/ethnic minority, adolesce

Results suggest inner-city parents respond to environmental risk, such that as neighborhood risk increases, so also do protective home and family management practices. Parent engagement in restricting alcohol access and improving family management practices may be key to preventive efforts to reduce alcohol use.

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Request Reprint E-Mail: alt@ichp.ufl.edu

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Individual and Contextual Effects of School Adjustment on Adolescent Alcohol Use

Prevention Science Published Online 26 Feb 2009

This paper examines the effect of a student’s own school adjustment as well as the contextual level of school adjustment (the normative level of school adjustment among students in a school) on students’ self-reported use of alcohol.

The results demonstrate the importance of both a student’s own level of school adjustment and the normative level of school adjustment among students in the school on an adolescent’s use of alcohol. Differences in school adjustment across schools were quite strongly related to an adolescent’s own alcohol use, indicating that school adjustment is an important aspect of school climate. Initiatives aimed at improving school climate may have beneficial effects on students’ alcohol use.

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Request Reprint E-Mail: kim.henry@colostate.edu

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BMA continues calls for minimum pricing and advertising ban

Last week the British Medical Association (BMA) annual conference passed a motion to continue calling for a minimum price and a ban on alcohol advertising. The decision comes as previous calls to introduce minimum pricing have been rejected by the government, with the Prime Minister arguing that they would not 'punish the sensible majority'. . . . . .

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Alcohol Consumption Indices of Genetic Risk for Alcohol Dependence

Biological Psychiatry Article in Press, 3 July 2009

Genetic influences accounted for 30%–51% of the variance in the alcohol measures and genetic correlations were .90 or higher for all measures, with the correlation between consumption and dependence symptoms among nondependent individuals estimated at .97 (95% confidence interval: .80–1.00).

Heaviness of consumption and AD symptoms have a high degree of genetic overlap even among nondependent individuals in the general population, implying that genetic influences on dependence risk in the general population are acting to a considerable degree through heaviness of use and that quantitative measures of consumption will likely have a useful role in the identification of genes contributing to AD.

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Request Reprint E-Mail: grantj@psychiatry.wustl.edu

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The δ1 Opioid Receptor Is a Heterodimer That Opposes the Actions of the δ2 Receptor on Alcohol Intake

Biological Psychiatry Article in Press 3 July 2009

We show that the subtypes of the δ receptor, δ1 and δ2, have opposing effects on ethanol consumption. We find that these effects are synergistic; thereby suggesting that δ1 and δ2 receptors are distinct molecular targets. Indeed, we provide both in vitro as well as in vivo evidence that the δ1 subtype is a μ-δ heterodimer and that the δ2 subtype is most likely a δ homomer.

Together these data provide insight into the limited actions of the clinically important drug naltrexone and identify a novel target with improved specificity and efficacy for the development of new therapeutics for the treatment of alcoholism.

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Request Reprint E-Mail: whistler@gallo.ucsf.edu

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The Impact of Alcohol in: Greater Manchester Fourth Quarter - May 2009

This report identifies available alcohol intelligence from across Greater Manchester. The data are separated into six categories: consumption, health related impacts of alcohol, crime, young people, and examples of interventions to tackle excessive alcohol consumption. The report contains the latest annual and quarterly data available. Where no updates have been published, the latest data published in the last quarterly report is still provided here for reference. Where data are new or updated, these are labelled as such throughout this report .

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Development and validation of the Alcoholics Anonymous Intention Measure (AAIM)

Drug and Alcohol Dependence Article in Press, 5 July 2009

Drop-out from 12-step groups is notoriously high, yet the field lacks strong models and scales for addressing this problem. We aim to determine whether the theory of planned behavior (TPB) can be applied to 12-step involvement, and to develop and validate a scale of 12-step readiness based on that theory: the Alcoholics Anonymous Intention Measure (AAIM).

Results generally support the TPB as a model of 12-step involvement and suggest specific targets for 12-step facilitation interventions within attitude, norm, and control components. Findings also support the AAIM as a tool for identifying drop-out risks and tailoring individual interventions.

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Request Reprint E-Mail: szemore@arg.org

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Measuring Liability for Substance Use Disorder among College Students: Implications for Screening and Early Intervention

The American Journal of Drug and Alcohol Abuse, Volume 35, Issue 4 July 2009 , pages 233 - 241

Heavy drinking and illicit drug use among college students has been a longstanding public health concern. Current methods to screen and identify college students at-risk for the development of substance use disorders (SUD) are somewhat limited.

This study aimed to cross-validate the work by Kirisci et al., who developed the Transmissible Liability Index (TLI), by deriving a set of items that would be potentially useful for characterizing SUD risk across multiple dimensions among college students.

The TLI-CV was significantly associated with baseline dependence and significantly higher for non-dependent individuals who later became dependent during the subsequent three years of college. These associations were observed for both sexes, Whites, Blacks/African-Americans, Asians, and other racial minorities. The sensitivity and specificity were suboptimal.

The TLI-CV advances prior research to identify college students at risk for SUD. This approach holds potential promise to identify and ultimately modify the trajectories of college students who may be at risk for the development of SUD.

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Request Reprint E-Mail: aarria@cesar.umd.edu

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Genome-wide Association Study of Alcohol Dependence

Arch Gen Psychiatry. 2009;66(7):773-784.

Alcohol dependence is a serious and common public health problem. It is well established that genetic factors play a major role in the development of this disorder. Identification of genes that contribute to alcohol dependence will improve our understanding of the mechanisms that underlie this disorder.

To identify susceptibility genes for alcohol dependence through a genome-wide association study (GWAS) and a follow-up study in a population of German male inpatients with an early age at onset.

This is the first GWAS and follow-up study to identify a genome-wide significant association in alcohol dependence. Further independent studies are required to confirm these findings.

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Request Reprint E-Mail: marcella.rietschel@zi-mannheim.de

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Ethanol-Modulated Camouflage Response Screen in Zebrafish Uncovers a Novel Role for cAMP and Extracellular Signal-Regulated Kinase Signaling in Behavioral Sensitivity to Ethanol

The Journal of Neuroscience, July 1, 2009, 29(26):8408-8418

Ethanol, a widely abused substance, elicits evolutionarily conserved behavioral responses in a concentration-dependent manner in vivo. The molecular mechanisms underlying such behavioral sensitivity to ethanol are poorly understood. While locomotor-based behavioral genetic screening is successful in identifying genes in invertebrate models, such complex behavior-based screening has proven difficult for recovering genes in vertebrates.

Here we report a novel and tractable ethanol response in zebrafish. Using this ethanol-modulated camouflage response as a screening assay, we have identified a zebrafish mutant named fantasma (fan), which displays reduced behavioral sensitivity to ethanol.

Positional cloning reveals that fan encodes type 5 adenylyl cyclase (AC5). fan/ac5 is required to maintain the phosphorylation of extracellular signal-regulated kinase (ERK) in the forebrain structures, including the telencephalon and hypothalamus. Partial inhibition of phosphorylation of ERK in wild-type zebrafish mimics the reduction in sensitivity to stimulatory effects of ethanol observed in the fan mutant, whereas, strikingly, strong inhibition of phosphorylation of ERK renders a stimulatory dose of ethanol sedating.

Since previous studies in Drosophila and mice show a role of cAMP signaling in suppressing behavioral sensitivity to ethanol, our findings reveal a novel, isoform-specific role of AC signaling in promoting ethanol sensitivity, and suggest that the phosphorylation level of the downstream effector ERK is a critical "gatekeeper" of behavioral sensitivity to ethanol.

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Request Reprint E-Mail: su.guo@ucsf.edu

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Persistent Deficits in Heart Rate Response Habituation Following Neonatal Binge Ethanol Exposure

Alcoholism: Clinical and Experimental Research1 Published Online: 10 Jun 2009

These data suggest that there are relatively long-term consequences of neonatal ethanol exposure on nonassociative memory. This impairment in habituation may be relevant to the distractibility and poor focused attention that is pervasive among humans diagnosed with fetal alcohol spectrum disorders.

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Request Reprint E-Mail: pshunt@wm.edu

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Alcohol Abuse Enhances Pulmonary Edema in Acute Respiratory Distress Syndrome

Alcoholism: Clinical and Experimental Research Published Online: 1 Jul 2009

Pulmonary edema is a cardinal feature of the life-threatening condition known as acute respiratory distress syndrome (ARDS). Patients with chronic alcohol abuse are known to be at increased risk of developing and dying from ARDS.

Based upon preclinical data, we hypothesized that a history of chronic alcohol abuse in ARDS patients is associated with greater quantities and slower resolution of pulmonary edema compared with ARDS patients without a history of alcohol abuse.

In patients who develop ARDS, alcohol abuse is associated with greater levels EVLW and a trend towards slower resolution of EVLW. Combined with mechanistic and preclinical evidence linking chronic alcohol consumption and ARDS, targeted therapies should be developed for these patients.

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Request Reprint E-Mail: greg.martin@emory.edu

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Upregulation of Serotonin Transporter by Alcohol in Human Dendritic Cells: Possible Implication in Neuroimmune Deregulationical
Alcoholism: Clinical and Experimental Research Published Online: 1 Jul 2009

Our study suggests that alcohol upregulates SERT and MAO-A by elevating cyclic AMP, which may lead to decreased concentration of 5-HT in the extracellular medium. As 5-HT is a major neurotransmitter and an inflammatory mediator, its alcohol-mediated depletion may cause both neurological and immunological deregulation.

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Request Reprint E-Mail: nairm@fiu.edu
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Alcohol-Induced Electrical Remodeling: Effects of Sustained Short-Term Ethanol Infusion on Ion Currents in Rabbit Atrium

Alcoholism: Clinical and Experimental Research Published Online: 1 Jul 2009

Sustained short-term ethanol infusion in rabbits alters atrial current densities. HHS might be favored by alcohol-induced atrial electrical remodeling.

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Request Reprint E-Mail: roman.laszlo@med.uni-tuebingen.de

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Modulation of Brain Endocannabinoid Levels by Voluntary Alcohol Consumption in Alcohol-Preferring AA Rats

Alcoholism: Clinical and Experimental Research Published Online: 1 Jul 2009

These results demonstrate that voluntary alcohol drinking modulates the levels of endocannabinoids in several brain areas implicated in alcohol reinforcement. AEA and 2-AG were differentially affected, suggesting that they could have partially separate modulatory roles. Alterations were more widespread in females than males, possibly reflecting their higher alcohol intake. Taken together, alcohol-induced release of endocannabinoids may have an important role in alcohol reinforcement and development of alcohol addiction.

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Request Reprint E-Mail: petri.hyytia@thl.fi

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A Single, Moderate Ethanol Exposure Alters Extracellular Dopamine Levels and Dopamine D2 Receptor Function in the Nucleus Accumbens of Wistar Rats
Alcoholism: Clinical and Experimental Research Published Online: 1 Jul 2009

The present results indicate that a single EtOH pretreatment at a moderate dose can increase DA neurotransmission in the NAc due, in part, to reduced D2 autoreceptor function.

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Request Reprint E-Mail: jmurphy1@iupui.edu
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Reduction of Alcohol's Reinforcing and Motivational Properties by the Positive Allosteric Modulator of the GABAB Receptor, BHF177, in Alcohol-Preferring Rats
Alcoholism: Clinical and Experimental Research Published Online: 1 Jul 2009

The present results extend to BHF177 the capacity of the 2 previously tested positive allosteric modulators of the GABAB receptor, CGP7930 and GS39783, to specifically suppress alcohol's reinforcing and motivational properties in alcohol-preferring rats.

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Rerquesty Reprint E-Mail: colomb@unica.it
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Social–cognitive correlates of protective drinking behaviors and alcohol-related consequenes in college students

Addictive Behaviors Article in Press 27 May 2009

Although heavy episodic drinkers are at risk to experience alcohol-related consequences, studies show that a large percentage of student drinkers do not experience problems as a result of their drinking.

The present study was a more in-depth examination of factors beyond just drinking quantity and frequency to explain why students experience consequences. The current research examined the relationship between the use of protective behaviors, alcohol use, and alcohol related consequences, as well as the relationship between attitudinal and cognitive predictors of engaging in protective behaviors when drinking.

We hypothesized there would be a significant direct effect of protective behaviors on consequences after taking into account the effect of alcohol use and that cognitive predictors, including perceived self-efficacy, perceived effectiveness, and subjective norm, would be associated with the attitude and frequency of engaging in protective behaviors.

Results supported both hypotheses, indicating good model fit for all models and significant paths between constructs .

These findings extend the literature on protective behaviors by providing insight as to their utility in preventing harm and why students choose to engage in these behaviors. Implications for interventions are also discussed.

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Request Reprint E-Mail: anneray@psu.edu

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