Interventions might offer a pregnant pause in addiction
Nature Medicine 14, 1168 (2008)

Doctors have known for decades that cigarettes and alcohol harm developing babies. Now, because many pregnant women find it difficult to beat these addictions, research has begun looking for ways to minimize their damage to the fetus.

. . . . .

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Effects of subunit selective nACh receptors on operant ethanol self-administration and relapse-like ethanol-drinking behavior
Psychopharmacology Online First 6 November 2008

The sensitivity to ethanol central effects is partially determined by the subunit composition of brain nicotinic acetylcholine receptors (nAChRs).

Thus, the effects of intraventral tegmental area (VTA) administration of the nicotinic subunit-specific antagonist, α-conotoxin MII (αCtxMII, α₃β₂*, β₃*, α₆*), were compared to those of systemic mecamylamine (MEC, an allosteric negative modulator of the nAChR), dihydro-β-erythroidine (DHβE, α₄β₂*), and methyllycaconitine (MLA, α₇*) to elucidate involvement of different subunits of nAChRs in operant ethanol self-administration and relapse-like activation of ethanol consumption after ethanol deprivation in rats.

αCtxMII reduced operant ethanol self-administration and blocked the deprivation-induced relapse-like ethanol consumption. MEC reduced operant ethanol self-administration and inhibited the deprivation-induced increase in alcohol consumption. DHβE did not alter ethanol self-administration in the lower-dose range but inhibited ethanol intake at a higher dose (4 mg/kg), although this effect might have been nonspecific. MLA failed to block self-administration of ethanol and relapse-like drinking after deprivation.

Our results indicate that nAChRs are involved in the modulation of operant alcohol self-administration and relapse-like alcohol drinking behavior in rats. Our observations support the working hypothesis that systemically active selective ligands for nAChR α₃β₂*, β₃, and/or α₆* receptor subunits might be of therapeutic value for the treatment of alcoholism.

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Family History of Alcohol Dependence and Initial Antidepressant Response to an N-methyl-D-aspartate Antagonist
Biological Psychiatry Article in Press 8 November 2008

A high rate of comorbidity exists between mood disorders and alcohol dependence. Furthermore, both ketamine, a dissociative anesthetic with a recently described rapid-onset antidepressant effect, and ethanol are N-methyl-D-aspartate (NMDA) receptor antagonists. Previous investigations of healthy individuals with a family history of alcohol dependence have found that these individuals have an attenuated response to ketamine's perceptual disturbance and dysphoric effects similar to that found in individuals with a self-reported history of alcohol dependence.

This study investigated whether a family history of alcohol dependence influences ketamine's initial antidepressant effect.

Twenty-six subjects with DSM-IV treatment-resistant major depression were given an open-label intravenous infusion of ketamine hydrochloride (.5 mg/kg) and rated using various depression scales at baseline, 40, 80, 120, and 230 min postinfusion. The primary outcome measure was Montgomery-Asberg Depression Rating Scale (MADRS) scores

Subjects with a family history of alcohol dependence showed significantly greater improvement in MADRS scores compared with subjects who had no family history of alcohol dependence.

A family history of alcohol dependence appears to predict a rapid initial antidepressant response to an NMDA receptor antagonist.

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Disruption of Orbitofrontal Cortex Laterality in Offspring from Multiplex Alcohol Dependence Families
Biological Psychiatry Article in Press, 4 november 2008

Increased susceptibility for developing alcohol dependence (AD) might be related to structural differences in brain circuits that influence the salience of rewards and/or modify the efficiency of information processing. The role of the orbitofrontal cortex (OFC) in regulating emotional processing is increasingly being recognized along with its association with impulsive behavior.

High-risk offspring from multiplex for AD families showed decreased right/left OFC volumes in comparison with control subjects. Smaller volume in the right hemisphere was significantly associated with variation in the 5-HTT and BDNF genes. White matter (WM) ratios showed a positive correlation with MPQ Control scale scores, indicating that reduced OFC WM is related to greater impulsivity.

Offspring from multiplex families for AD manifest genetic susceptibility by exhibiting disruption in the laterality of the OFC volume that is related to greater impulsivity (lower Control scale scores). This disruption in OFC laterality is related to variation in genes associated with neuronal growth.

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Induction of brain CYP2E1 changes the effects of ethanol on dopamine release in nucleus accumbens shell
Drug and Alcohol Dependence Article in Press, 6 November 2008


CYP2E1 is an important enzyme involved in the brain metabolism of ethanol that can be induced by chronic consumption of alcohol. Recent works have highlighted the importance of this system in the context of the behavioural effects of ethanol. Unfortunately, the underlying neurochemical events for these behavioural changes, has not been yet explored.

In this work, we have started this exploration by analyzing the possible changes in the neurochemical response of the mesolimbic system to ethanol after pharmacological induction of brain CYP2E1.

We have used the dopamine extracellular levels in nucleus accumbens (NAc) core and shell, measured by means of microdialysis in vivo, as an index of the effects of ethanol. Acetone 1% in the tap water was used to induce brain CYP2E1. Efficacy of the induction protocol was assessed by immunoblotting.

Intravenous administration of 1.5 g/kg of ethanol in control rats provoked a significant increase of the dopamine levels in both the core (up to 127% of baseline) and the shell (up to 122% of baseline) of the NAc. However, the same dose of ethanol in acetone-treated rats only increased the dopamine extracellular levels in the core (up to 142% of baseline) whereas dopamine levels in the shell subregion remain unaltered relative to baseline.

The results of this study indicate that induction of CYP2E1 changes the response of the mesolimbic system to ethanol in a region-dependent manner. Two hypotheses are postulated to explain the observed effects.

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N²-Ethyldeoxyguanosine as a Potential Biomarker for Assessing Effects of Alcohol Consumption on DNA
Cancer Epidemiology Biomarkers & Prevention 17, 3026-3032, November 1, 2008


Head and neck cancers are causally related to alcohol consumption, but the underlying mechanisms are unclear. Ethanol is metabolized to acetaldehyde, an experimental carcinogen. Quantitation of the major DNA adduct of acetaldehyde, N²-ethylidenedeoxyguanosine, in human tissues could help to elucidate the mechanism of alcohol carcinogenicity.

We applied a quantitative method for the analysis of this adduct, measured as the NaBH₃CN reduction product N²-ethyldeoxyguanosine (N²-ethyl-dGuo) by liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring, on DNA (0.04 ± 0.03 mg) isolated from blood collected from control subjects recruited from two studies conducted in different areas of Europe between 1999 and 2005. The group selected from the first study (n = 127) included alcohol drinkers and abstainers while the group from the second study (n = 50) included only heavy drinkers. N²-ethyl-dGuo was detected in all DNA samples.

After adjusting for potential confounders, in the first study, drinkers showed a higher level of N²-ethyl-dGuo (5,270 ± 8,770 fmol/µmol dGuo) compared with nondrinkers (2,690 ± 3040 fmol/µmol dGuo; P = 0.04). A significant trend according to dose was observed in both studies (P = 0.02 and 0.04, respectively). Taking into account the amount of alcohol consumption, adduct levels were higher in younger compared with older subjects (P = 0.01), whereas no differences were observed comparing men with women.

These results show the feasibility of quantifying N²-ethyl-dGuo in small-volume blood samples and are consistent with the hypothesis that ethanol contributes to carcinogenesis through DNA adducts formation.

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Multiple indicator hidden Markov model with an application to medical utilization data
Statistics in Medicine Published Online: 7 Nov 2008

Monthly counts of medical visits across several years for persons identified to have alcoholism problems are modeled using two-state hidden Markov models (HMM) in order to describe the effect of alcoholism treatment on the likelihood of persons to be in a healthy or unhealthy state.

The medical visits can be classified into different types leading to multivariate counts of medical visits each month. A multiple indicator HMM is introduced, which simultaneously fits the multivariate Poisson counts by assuming a shared hidden state underlying all of them. The multiple indicator HMM borrows information across different types of medical encounters. A univariate HMM based on the total count across types of medical visits each month is also considered.
Comparisons between the multiple indicator HMM and the total count HMM are made, as well as comparisons with more traditional longitudinal models that directly model the counts.

A Bayesian framework is used for the estimation of the HMM and implementation is in Winbugs

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Request Reprint E-Mail: melanie@biostat.umn.edu
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Commission on Social Determinants of Health - Final Report

Closing the gap in a generation: Health equity through action on the social determinants of health

Social justice is a matter of life and death. It affects the way people live, their consequent chance of illness, and their risk of premature death. We watch in wonder as life expectancy and good health continue to increase in parts of the world and in alarm as they fail to improve in others.

pg. 135
There are nearly 2 million alcohol-related deaths per year, of the same order as HIV/AIDS at 2.9 million. Absolute levels of alcohol-related disease and disability are as high in the poorest countries of Africa and America as in Western Europe and North America. Alcohol-related disease is highest in the former Soviet Union and Central Asia, amounting to 13% of the total burden. In the Russian Federation itself it is even higher (PPHCKN, 2007b). A society without effective alcohol policies is likely to experience a sharp rise in alcohol problems during economic development. The transition in the former Soviet Union is a striking example. In the Russian Federation, the ‘shock therapy’ and economic liberalization in 1992 included a total deregulation of trade in alcoholic beverages. The subsequent mortality rise in the Russian Federation has been linked to a rise in binge drinking of alcohol (Leon et al., 1997;
PPHCKN, 2007b).

pg. 142
Learning from the FCTC, the Commission urges WHO to initiate a discussion with Member States on regulatory action for alcohol control (Boxes 12.18 and 12.19). The WHO European Region suffers the highest levels of alcoho lrelated disease and violence, with very large differences in alcohol-related mortality between countries. European policy discussion has been characterized by a conflict of view: is alcohol a commodity like any other, or should it be seen as a public health concern, whose trade could be regulated to protect people’s health? The Commission urges governments in the WHO European Region and globally to work together to limit alcohol-related harm

Executive summary (PDF)

Download the full report (PDF)
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Editorials - International regulation of alcohol
BMJ 2008;337:a2364

A framework convention is needed, as for tobacco control

The World Health Organization’s Commission on Social Determinants of Health has just issued its main report,¹ which lays out an ambitious programme of actions to tackle health inequity. The commission notes the substantial contribution of alcohol to injury, disease, and death worldwide,² and it proposes that WHO and member nations should use the 2005 framework convention on tobacco control as a model for alcohol control. We agree that it is time to adopt such a framework. The commission’s work underscores the urgent need for international agreements that promote alcohol controls throughout the developing and developed world. Increasing affluence in the fastest developing regions of the world—East Asia, the Pacific region, and South Asia—has led to increased alcohol consumption, along with a higher burden of harm caused by alcohol. These increases foreshadow future trends in consumption and harm for other developing countries—such as those in Africa, Central America, and South America
. . . . .

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Request Reprint E-Mail: RobinR@turningpoint.org.au
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Alcohol Taxes and Fees: An economic and historical perspective

Testimony from Bruce Lee Livingston, MPP
Executive Director, Marin Institute
Assembly Select Committee on Alcohol and Drug Abuse
Thursday, March 6, 2008

I am going to give a brief history of alcohol tax and fee proposals, compare California’s tax rates to other states, present alcohol cost and harm data, and then run through a few tax and fee options that could generate hundreds of millions, if not billions, of dollar.
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Press Release - Nickel a Drink to Save State Budgets

Marin Institute Calls on States with Budget Shortfalls to Follow California in Proposing an Alcohol Tax Increase

Long Overdue Tax Increases Could Ease Budget Deficits in 39 States and Mitigate Alcohol-Related Costs

SAN RAFAEL, CA (November 7, 2008) – Public health advocates are calling on policymakers around the nation to follow the lead of California Governor Arnold Schwarzenegger to help fund ailing state budgets through higher alcohol taxes. On Thursday, Governor Schwarzenegger proposed a nickel a drink tax increase on beer, wine, and distilled spirits to help reduce California’s budget shortfall, while providing critical support to the state’s programs that reduce alcohol-related problems.

At least 38 other states also face serious budget deficits, totaling more than $60 billion dollars, according to the Center on Budget and Policy Priorities. “A nickel a drink -- It’s the change we need to fix budgets around the nation,” said Bruce Lee Livingston, executive director of Marin Institute, the California-based alcohol industry watchdog. “The largest states, such as New York and Florida can avoid cutting essential programs through long-overdue alcohol tax increases,” Livingston added. California’s proposal accomplishes exactly that.
. . . . . .

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Governor Schwarzenegger Proposes an Alcohol Tax Increase

California Governor Schwarzenegger has proposed a nickel a drink alcohol tax increase on wine, beer and distilled spirits to take effect January 1, 2009. The long overdue tax increase will raise new funds – estimated at over $878 million over the next year and a half - to help reduce the state’s serious budget shortfall while providing critical support to programs that deal specifically with alcohol-related problems.

SEE BUDGET PROPOSAL see pg. 12

The last alcohol tax increase in California was in 1992, and was only a penny on a glass of wine and two cents per can of beer and shot of spirits. Since that time, rising inflation has led to a 49% net decrease in state alcohol taxes. At the same time, alcohol-related problems have increased dramatically and now cost the state and its citizens $38 billions dollars annually in healthcare, criminal justice, addiction treatment, lost productivity and myriad other costs.

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Press Release - Governor Schwarzenegger Announces Plan to Address Budget Emergency, Stimulate California’s Economy
11/06/20

To remedy California's urgent budget situation due to economic conditions radically deteriorating since the 2008 Budget Act was signed, Governor Arnold Schwarzenegger today called a special session of the legislature and announced an action plan to get our budget back on track, invigorate our economy and generate jobs for the state's unemployed. The Governor called for a combination of cuts and revenue increases to solve California's budget shortfall which has now reached $11.2 billion. The actions prescribed by the Governor must be taken up as quickly as possible in order to prevent a cash crisis that will jeopardize vital state services.

. . . . .Additionally, the Governor called for additional revenue increases including broadening the sales and use tax to include certain services, imposing an oil severance tax upon any oil producer that extracts oil from the earth or water in this state and increasing the alcohol excise tax by five cents a drink.

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Recollective experience in alcohol dependence: a laboratory study
Addiction Volume 103 Issue 12, Pages 1969 - 1978


Alcohol dependence has been linked to dysfunction of fronto-temporo-striatal circuits which mediate memory and executive function. The present study aimed to explore the specificity of recognition memory changes in alcohol dependence.

Alcohol-dependent patients showed intact hit rates, but increased false alarm rates and an impaired ability to remember the learning context. Both the DPSD model and PDP estimates yielded significantly reduced recollection estimates in the alcohol-dependent compared to control subjects. Whether or not familiarity was impaired, depended upon the sensitivity of the estimation procedure.

Taken together, the result pattern suggests a significant impairment in recollection and mild familiarity changes in recently detoxified, predominantly male, alcohol-dependent subjects.

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Alcohol consumption and mortality and hospital admissions in men from the Midspan Collaborative cohort study
Addiction Volume 103 Issue 12, Pages 1979 - 1986


To investigate the relationships between alcohol consumption and mortality and morbidity risk by specific causes.

Mortality risk was increased for men drinking 15–21 or more units per week for all causes, stroke, liver disease and alcohol-related causes. For respiratory mortality, drinkers of 35 or more units had double the risk compared to non-drinkers. CHD mortality showed increasing trends with consumption when adjusted for age and after full adjustment showed no clear patterns, although the 8–14 units group had a lower risk than non-drinkers [relative rate 0.81 (0.68–0.97)]. Hospital admissions had similar patterns to mortality for stroke and liver disease. Increased risk began at 8–14 units for alcohol-related admissions, and at 15–21 units for respiratory admissions. Non-drinkers had higher risks of having a CHD admission than drinkers and there were decreasing trends with increasing consumption (P = 0.019).

Consumption of 15–21 units per week and over was associated with increased mortality from most causes and increased risk of hospital admissions from stroke, liver disease and respiratory diseases. Alcohol-related admissions were raised from 8 to 14 units. Alcohol use may have been under-reported in our study, but it was similar to other studies of the time. The apparent protective effect of alcohol with CHD admissions could be due partly to detrimental effects of heavy drinking causing sudden deaths. The associations, including that with respiratory disease, may arise from inadequate adjustment for confounding by other factors such as smoking.

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Recovery Capital: A Primer for Addiction Professionals

Written by William L. White, MA and William Cloud, PhD

Thursday, 06 November 2008 The history of addiction treatment in America contains within it a history of key ideas that have transformed service philosophies and practices. In the early history of modern treatment, for example, chemical dependency emerged as a core idea that helped integrate what were then two separate fields: one focused on alcoholism; the other on drug addiction. Other concepts, such as codependency, dual diagnosis, gender-specific, developmental appropriateness, cultural competence, trauma-informed, evidence-based, stages of change, motivational enhancement, recovery management and recovery coaching helped, or are now helping, transform addiction treatment into a more person-centered, holistic, family-centered and recovery-focused system of care. Addiction professionals across America are witnessing the field’s paradigmatic shift from a pathology and intervention focus to a recovery focus (White, 2004; 2005). Attention on the lived solution to alcohol and other drug (AOD) problems is reflected in the growing interest in defining recovery; conducting recovery prevalence surveys; illuminating the varieties of recovery experiences; and mapping the patterns, processes, and stages of long-term recovery (Betty Ford Institute Consensus Panel, 2007; White & Kurtz, 2006). One of the key ideas at the core of this shift is that of recovery capital (RC). This article defines RC and explores how attention to RC can be integrated into the service practices of front-line addiction professionals. . . . . . . Read Full Article ________________________________________________

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Influences of Gender and Age on Relationships Between Alcohol Drinking and Atherosclerotic Risk Factors
Alcoholism: Clinical and Experimental Research Published Online: 5 Nov 2008


Alcohol drinking affects atherosclerotic progression mainly through blood pressure and lipid metabolism. The purpose of the present study was to clarify whether effects of alcohol drinking on atherosclerotic risk factors differ by gender and age.

The mean level of body mass index (BMI) was slightly but significantly lower in drinkers than in nondrinkers in the thirties, forties, and fifties age groups in men and in the twenties, thirties, forties, and fifties age groups in women, while this tendency was not found in the sixties age groups of men and women. In men, mean blood pressure was higher in moderate-to-heavy drinkers than in nondrinkers in all age groups and was higher in light drinkers than in nondrinkers only in the age groups after 40 years. Mean blood pressure of women was higher in the moderate-to-heavy drinker group than in the nondrinker group and this difference became higher with advance of age. In women, mean blood pressure was not affected by light drinking in any of the age groups except for the fifties age group. In men, serum total cholesterol was higher in drinkers than in nondrinkers in the twenties age group but was lower in drinkers than in nondrinkers at thirties or older. Serum total cholesterol in women was lower in drinkers than in nondrinkers in the age groups from twenties to forties but tended to be higher in drinkers than in nondrinkers in the sixties age group. Serum HDL cholesterol increased with advance of age from thirties to sixties in men, while it decreased with advance of age from twenties to sixties in women. Serum HDL cholesterol was higher in drinkers than in nondrinkers in all age groups of men and women, and atherogenic index, calculated by using serum total cholesterol and HDL cholesterol concentrations, was lower in drinkers than in nondrinkers in all age groups of men and women.

Both in men and women, blood pressure and HDL cholesterol were strongly affected by alcohol drinking: the elevating effect of alcohol drinking on blood pressure was more prominent in the elderly than in the young, while the elevating effect of alcohol drinking on serum HDL cholesterol was not influenced by age. Relationships of drinking with total cholesterol and BMI vary by age and gender.

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Association Analyses of Genetic Polymorphisms of GSTM1, GSTT1, NQO1, NAT2, LPL, PRSS1, PSTI, and CFTR With Chronic Alcoholic Pancreatitis in Japan

Alcoholism: Clinical and Experimental Research Published Online: 5 Nov 2008

Excessive consumption of alcohol is involved in the onset of pancreatitis. However, most of heavy drinkers do not always develop chronic pancreatitis. Various genetic factors appear to be involved in these individual differences in onset of chronic alcoholic pancreatitis. Here we investigated a possible association of alcoholic pancreatitis with polymorphisms of the various genes belong to the phase II detoxification enzymes responsible for metabolism of the oxidative compounds, and the several genes that have relevance to inherited pancreatitis.

Frequencies of the gene deletion of GSTM1 and GSTT1 in addition to the C-allele frequency of NQO1 tended to be higher in the alcoholic patients with (AlCP) or without pancreatic dysfunction (Alc) than in the healthy controls although the difference was not significant. The NAT2 gene showed no relation with Alc and AlCP patients. PSTI, LPL, PRSS1, and CFTR genes presented no association with chronic alcoholic pancreatitis.

All genes analyzed in the present study lacked association with chronic alcoholic pancreatitis. However, the gene deletion of GSTM1 and GSTT1, and the C-allele of NQO1 cannot be ruled out for association with alcoholism.

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Request Reprint E-Mail: maruyaka@kurihama.hosp.go.jp

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Decrease in the Prevalence of Adolescent Alcohol Use and its Possible Causes in Japan: Periodical Nationwide Cross-Sectional Surveys
Alcoholism: Clinical and Experimental Research Published Online:3 Nov 2008


Trends in alcohol drinking prevalence were assessed among Japanese adolescents, and possible reasons for a decrease in drinking prevalence observed in 2004.

The drinking prevalence in 2004 was decreased in comparison to that in 1996 and 2000 in both sexes and in all school grades. The current drinking rate (monthly drinker) among junior high school boys was 29.4% in 1996, 29.0% in 2000, and 20.5% in 2004, while that among senior high school boys was 49.7%, 48.7%, and 36.2%, respectively. The respective prevalence among junior and senior girls was 24.0%, 25.5%, and 20.0% and 40.8%, 42.1%, and 34.1%. The prevalent sources of alcohol beverages were searching in home, stores (convenience store, supermarket, or gas-stand), liquor shops, and bars.

An analysis of the reasons for this decrease identified a decrease in drinking prevalence in students' families, especially by fathers and older

A decrease in drinking prevalence of male family members and a limitation of sources of alcoholic beverages may contribute to the decrease in adolescent drinking prevalence.

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Request Reprint E-Mail: yoneatsu@grape.med.tottori-u.ac.jp

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Dietary patterns for reducing cardiovascular disease risk among Thai alcohol drinkers
Nutrition & Dietetics Volume 65 Issue 4, Pages 272 - 278

To study alcohol consumption patterns and dietary patterns among Thai people living in provinces with high risk of cardiovascular disease.

A cross-sectional survey was applied using a face-to-face interview. A total of 1698 respondents aged 15–59 years participated. Four provinces from northern, central, eastern and southern Thailand as well as Bangkok were selected.

A total of 724 (42.6%) men and 974 (57.4%) women participated in the study. There were more unhealthy habits associated with increased cardiovascular disease risk in the regular alcohol drinker group than in the occasional drinker and non-drinker groups. There were differences in diet practices between men and women.

Both men and women in the regular alcohol drinker group consumed highly salty food regularly 2.05 and 2.25 times more often than those in the occasional and non-drinker group. They also regularly added fish sauce to ready cooked food 1.57 and 3.62 times more often than the occasional and non-drinker group. Men in the regular alcohol drinker group regularly consumed deep-fried food 1.97 times more often than those in the occasional and non-drinker group. Men in the occasional and non-drinker group regularly consumed fibre food 1.69 times more than those in the regular drinker group.

These results showed that alcohol drinkers also consumed poor diets that may put them at risk of development of cardiovascular disease. Programs aimed at increasing knowledge concerning better nutrition and fostering healthy eating habits among alcohol drinkers are warranted.

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Request Reprint E-Mail: phjsw@mahidol.ac.th

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The NIfETy Method for Environmental Assessment of Neighborhood-level Indicators of Violence, Alcohol, and Other Drug Exposure
Prevention Science Volume 9, Number 4 / December, 2008 pp.245-255

There are limited validated quantitative assessment methods to measure features of the built and social environment that might form the basis for environmental preventive interventions.

This study describes a model approach for epidemiologic assessment of suspected environmental determinants of violence, alcohol and other drug (VAOD) exposure and fills this gap in current research.

The investigation sought to test the feasibility of a systematic and longitudinal assessment of residential block characteristics related to physical and social disorder and indicators of VAOD exposure. Planometric data were used to establish a stratified random sample of street segments within defined neighborhoods of an urban metropolitan area. Field rater assessments of these neighborhood street segments were conducted using the Neighborhood Inventory for Environmental Typology (NIfETy).

This report provides a detailed description of the NIfETy Method, including metric properties of the NIfETy Instrument and outcomes of training procedures and quality control measures. Also presented are block-level characteristics and estimates of observable signs of VAOD activity.

This work is a first step toward developing future community-level environmental preventive interventions geared to reduce community VAOD exposure among youthful urban populations and may prove to be useful to other public health research groups as well.

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Request Reprint E-Mail: dholden@jhsph.edu
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Alcohol self-administration acutely stimulates the hypothalamic-pituitary-adrenal axis, but alcohol dependence leads to a dampened neuroendocrine state.
European Journal of Neuroscience Volume 28 Issue 8, Pages 1641 - 1653


Clinical studies link disruption of the neuroendocrine stress system with alcoholism, but remaining unknown is whether functional differences in the hypothalamic-pituitary-adrenal (HPA) axis precede alcohol abuse and dependence or result from chronic exposure to this drug.

Using an operant self-administration animal model of alcohol dependence and serial blood sampling, we show that long-term exposure to alcohol causes significant impairment of HPA function in adult male Wistar rats.

Acute alcohol (voluntary self-administration or experimenter-administered) stimulated the release of corticosterone and its upstream regulator, adrenocorticotropic hormone, but chronic exposure sufficient to produce dependence led to a dampened neuroendocrine state.

HPA responses to alcohol were most robust in 'low-responding' non-dependent animals (averaging < 0.2 mg/kg/session), intermediate in non-dependent animals (averaging ∼0.4 mg/kg/session), and most blunted in dependent animals (averaging ∼1.0 mg/kg/session) following several weeks of daily 30-min self-administration sessions, suggesting that neuroendocrine tolerance can be initiated prior to dependence and relates to the amount of alcohol consumed.

Decreased expression of corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus of the hypothalamus and reduced sensitivity of the pituitary to CRF may contribute to, but do not completely explain, neuroendocrine tolerance.

The present results, combined with previous studies, suggest that multiple adaptations to stress regulatory systems may be brought about by excessive drinking, including a compromised hormonal response and a sensitized brain stress response that together contribute to dependence.

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Request Reprint E-Mail: hrichardson@cns.umass.edu
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Identification of a BK channel auxiliary protein controlling molecular and behavioral tolerance to alcohol
PNAS Published online before print November 3, 2008



Tolerance, described as the loss of drug effectiveness over time, is an important component of addiction. The degree of acute behavioral tolerance to alcohol exhibited by a naïve subject can predict the likelihood of alcohol abuse. Thus, the determinants of acute tolerance are important to understand. Calcium- and voltage-gated (BK) potassium channels, consisting of pore forming α and modulatory β subunits, are targets of ethanol (EtOH) action.

Here, we examine the role, at the molecular, cellular, and behavioral levels, of the BK β4 subunit in acute tolerance.

Single channel recordings in HEK-293 cells show that, in the absence of β4, EtOH potentiation of activity exhibits acute tolerance, which is blocked by coexpressing the β4 subunit. BK channels in acutely isolated medium spiny neurons from WT mice (in which the β4 subunit is well-represented) exhibit little tolerance.

In contrast, neuronal BK channels from β4 knockout (KO) mice do display acute tolerance. Brain slice recordings showed tolerance to EtOH's effects on spike patterning in KO but not in WT mice. In addition, β4 KO mice develop rapid tolerance to EtOH's locomotor effects, whereas WT mice do not.

Finally, in a restricted access ethanol self-administration assay, β4 KO mice drink more than their WT counterparts.

Taken together, these data indicate that the β4 subunit controls ethanol tolerance at the molecular, cellular, and behavioral levels, and could determine individual differences in alcohol abuse and alcoholism, as well as represent a therapeutic target for alcoholism.

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Is It Important to Prevent Early Exposure to Drugs and Alcohol Among Adolescents?

Psychological Science Volume 19 Issue 10, Pages 1037 - 1044


Exposure to alcohol and illicit drugs during early adolescence has been associated with poor outcomes in adulthood. However, many adolescents with exposure to these substances also have a history of conduct problems, which raises the question of whether early exposure to alcohol and drugs leads to poor outcomes only for those adolescents who are already at risk.

In a 30-year prospective study, we tested whether there was evidence that early substance exposure can be a causal factor for adolescents' future lives.

After propensity-score matching, early-exposed adolescents remained at an increased risk for a number of poor outcomes. Approximately 50% of adolescents exposed to alcohol and illicit drugs prior to age 15 had no conduct-problem history, yet were still at an increased risk for adult substance dependence, herpes infection, early pregnancy, and crime.

Efforts to reduce or delay early substance exposure may prevent a wide range of adult health problems and should not be restricted to adolescents who are already at risk.

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Request Reprint E-Mail: codgers@uci.edu.
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News Release - Revealed: alcohol's relentless grasp on women

Date: 03/11/2008

New research from the University of Western Sydney has revealed that women in recovery from alcoholism are at a high risk of relapsing as they reach midlife.

PhD researcher Ms Janice Withnall, from the UWS School of Eduction, has just completed the first three years of her Australia-wide study of the experiences of women who are recovering from alcohol dependency.

The results reveal that women recovering from alcoholism require many years of treatment and self-managed care; and the pressures imposed on many of these women as they reach midlife can impair their recovery abilities.

. . . . .

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Alcohol price link report due this month

4 November, 2008

By James Wilmore

Second part of Sheffield University study could be green light for governement to act on promotions

The delayed second part of an academic study examining the link between alcohol price and consumption is due for release by the government this month.

The first part of the Sheffield University report, released in July with the Safe, Sensible, Social consultation, concluded that “harmful” drinkers are influenced by price.

If the second part follows this line, it could be used by the government as the final green light to act on cheap promotions, in the on and off-trade.

. . . . . .

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News Release - New fast track help for areas with most severe alcohol problems

Wednesday 5 November 2008 10:29

Twenty of the areas worst hit by alcohol misuse are to receive support as part of a new programme which will help the local health service better identify and intervene with those at risk, Public Health Minister Dawn Primarolo announced today.

Speaking at the National Alcohol Conference in Nottingham, Ms Primarolo announced a new, wide-reaching Alcohol Improvement Programme to accelerate progress on reducing alcohol-related harm.

The new programme, backed by £6 million will:

* establish regional alcohol managers to push forward alcohol treatment and advice at a local level;
* pull together local information on statistics, hospital admissions and medical conditions to help treatment commissioners;
* help increase access to specialist treatment - there is currently just one place for every 18 people who show signs of dependence; and
* push out simple advice which, nationally, could help 250,000 men and 70,000 women to bring their drinking down to lower risk levels.

The twenty areas are some of the most deprived in the country and are most seriously affected by alcohol-related harm. Reducing alcohol problems is key to reducing inequality - these areas will be the first to take bold steps and get to grips with the problem.

An additional £1 million will fund a new Alcohol Learning Centre and support activities. The programme will draw together best practice and success from each of the 20 areas so other local health services can learn from the programme.

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Media Release - BC Trends In Alcohol And Drug Use

New report reveals harms caused by substance use

The use of alcohol and illicit drugs is sending more and more people to hospital, according to a new report by the University of Victoria’s Centre for Addictions Research of BC (CARBC).

The report, Regional Variations and Trends in Substance Use and Related Harms in BC, also shows that alcohol causes more than twice as many deaths as all major illicit drugs combined, while tobacco causes the most deaths—25 times that caused by illicit drugs. Vancouver Coastal Health has the highest rate of hospital stays caused by illicit drugs and the lowest for alcohol. The situation is reversed, however, for Northern Health.
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New CARBC Bulletin - Regional Variations and Trends in Substance Use & Related Harm in BC


Understanding regional variations and trends in drug use and related harms is an essential component of understanding alcohol and drug problems in BC and targeting resources to be of greatest benefit.

This bulletin will outline emerging trends and regional variations by health authority in BC using information collected through The BC Alcohol and Other Drug (AOD) Monitoring Project. The AOD project draws from a range of complementary data sources in a comprehensive approach to epidemiological monitoring of alcohol and other drugs use and related harms in BC, including: high-risk population surveys, seized drug analysis, alcohol sales records, and death and hospitalization records.

From this information, it is becoming increasingly apparent that use of alcohol and other drugs is characterized by marked regional variation and, in many cases, increasing trends. Furthermore, there are a substantial number of deaths and hospitalizations in BC that can be directly attributed to alcohol and other drugs


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ALCOHOL CONCERN NEWS 3 November 2008

• ALL PARTY PARLIAMENTARY GROUP INQUIRY INTO ALCOHOL TREATMENT

• ALCOHOL CONCERN MEMBERS/NON-MEMBERS TREATMENT FORUMS

• SERVICE USER ADVOCACY RESEARCH

• SAFE. SENSIBLE. SOCIAL – CONSULTATION

• YOUTH PROJECTS ON HUBCAPP

• EMBRACE – ACTING TOGETHER ON ALCOHOL, FAMILIES AND DOMESTIC VIOLENCE

• CONFERENCES, TRAINING AND SEMINARS

• ALCOHOL CONCERN ANNUAL CONFERENCE AND AG

• OTHER NEWS

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Press Release - US Hispanics prefer beer

Despite the considerable and growing numbers of Hispanics living in the United States, little is known about their alcohol-beverage preferences. A new study of U.S. Hispanics belonging to four national groups – Mexican American, Puerto Rican, Cuban American, and South/Central American – has found that beer is their beverage of choice.

Results will be published in the January issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"Currently, there is not much information about beverage preference among Hispanics and how that differs across national groups," said Raul Caetano, professor of epidemiology and regional dean (Dallas) at The University of Texas School of Public Health, as well as the study's corresponding author. "This is important to know because once we can identify a type of beverage that is more associated with risky drinking – such as binge drinking – then prevention policies can be developed to target that beverage and that type of drinking."

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Press Release - Greater alcohol outlet density is linked to male-to-female partner violence

Researchers know that the number of alcohol outlets in a given geographic area, referred to as alcohol-outlet density (AOD), is associated with a number of adverse health and social consequences. A new study of the relationship between AOD and intimate partner violence (IPV) – both male-to-female partner violence (MFPV) and female-to-male partner violence (FMPV) – has found that MFPV is more likely in neighborhoods where more alcohol is sold through liquor stores, bars, restaurants and other drinking places.

Results will be published in the January issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"We had detailed data on IPV in couples," explained Christy McKinney, faculty associate at the University of Texas School of Public Health, Dallas Regional Campus as well as corresponding author for the study. "By linking this information to AOD, we were ideally situated to address an understudied question using individual and couple-level data. We thought that greater alcohol availability could increase drinking which, in turn, could increase IPV."
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Press Release - Substance abuse and other psychiatric disorders are common among French prisoners