Dopamine and Ethanol Cause Translocation of PKC Associated with RACK: Cross-talk Between PKA and PKC Signaling Pathways
Molecular Pharmacology Fast Forward
First published on January 17, 2008;

Previously we found that neural responses to ethanol and the dopamine D2 receptor (D2) agonist NPA involve both epsilon protein kinase C (PKC) and cAMP-dependent protein kinase A (PKA). However, little is known about the mechanism underlying ethanol- and D2-mediated activation of PKC and the relationship to PKA activation.

In the present study, we used a new PKC antibody, 14E6, that selectively recognizes active PKC when not bound to its anchoring protein RACK (receptor for activated C-kinase), and PKC isozyme-selective inhibitors and activators, to measure PKC translocation and catalytic activity.

We show here that ethanol and NPA activated PKC and also induced translocation of both PKC and its anchoring protein, RACK to a new cytosolic site. The selective PKC agonist, pseudo-RACK, activated PKC but did not cause translocation of the PKC/RACK complex to the cytosol.

These data suggest a step-wise activation and translocation of PKC following NPA or ethanol treatment where PKC first translocates and binds to its RACK and subsequently the PKC/RACK complex translocates to a new subcellular site. Direct activation of PKA by Sp-cAMPS, PGE1 or the adenosine A2A receptor is sufficient to cause PKC translocation to the cytosolic compartment in a process that is dependent on PLC activation and requires PKA activity.

These data demonstrate a novel cross-talk mechanism between PKC and PKA signaling systems. PKA and PKC signaling have been implicated in alcohol rewarding properties in the mesolimbic dopamine system.

Cross-talk between PKA and PKC may underlie some of the behaviors associated with alcoholism.

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Alcohol and Malt Liquor Availability and Promotion and Homicide in Inner Cities
Substance Use & Misuse, Volume 43, Issue 2 January 2008 , pages 159 - 177

We investigated the role of the alcohol environment in explaining disparities in homicide rates among minorities in 10 cities in the United States using 2003 data from the Malt Liquor and Homicide study.

We found that higher concentrations of African Americans were associated with higher homicide rates as well as greater alcohol availability, especially malt liquor availability. The promotion of malt liquor on storefronts was also significantly greater in African American than in other neighborhoods.

However, none of the measures representing alcohol or malt liquor availability and promotion variables changed the effect of neighborhood racial/ethnic concentration on homicide.

Limitations and implications of our findings are discussed.

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Request Reprint E-Mail: jones010@umn.edu
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Illicit Alcohol Consumption and Neuropathy – A Preliminary Study in Sri Lanka
Alcohol and Alcoholism Advance Access published online on January 18, 2008



To compare the effects on peripheral and autonomic nerve functions of Sri Lankan illicitly distilled alcohol consumption versus legal spirit consumption.

Lower-limb motor and sensory nerve conduction parameters were affected in both groups of alcoholics. When compared with controls, in illicit spirit drinkers the mean heart rate indexes of all parasympathetic tests were lower while in legal spirit drinkers the heart rate response to standing was affected. There were no differences in the results of the above tests when the two groups of heavy drinkers were compared.

Though chronic alcoholism results in peripheral and autonomic nerve damage, the damage caused by consumption of illicitly distilled spirit is not worse than the damage caused by consumption of legal spirits.

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Request Reprint E-Mail: himanif@mfac.kln.ac.lk

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African Americans Complete Alcohol Treatment at Lower Rates than Whites

	Vol. 3, No. 1, 2008
African Americans Complete Alcohol Treatment at Lower Rates than Whites Alcohol-related health problems are two to five times as prevalent among ethnic and racial minorities as they are among whites, despite similar lifetime prevalences of frequent problem drinking. The reasons for this have not been well understood, although they have obvious implications for reducing racial and ethnic health disparities—a national priority. RAND DPRC undertook a series of analyses to shed light on one possible contributor to the disparity in alcohol-related health problems: differences between white and minority alcohol treatment outcomes. The analyses were performed on intake and discharge records from all publicly funded outpatient and residential alcohol treatment recovery programs in Los Angeles County from 1998 to 2000. Sophisticated statistical analyses were used to isolate the contributions of different factors to the problem. These are a few of the major findings: African Americans complete treatment at lower rates than whites (18 vs. 27 percent outpatient; 31 vs. 46 percent residential), whereas Hispanics and whites complete treatment at similar rates (see the graph). Forty percent of the outpatient treatment completion disparity between African Americans and whites could be explained by patient characteristics, particularly economic resources; only 7 percent of the residential disparity could be so explained. Approximately a third of the outpatient treatment completion disparity could be explained by differences in the neighborhoods of the treatment facilities attended by African Americans vs. whites. African Americans and Hispanics are much less likely to receive residential treatment (as opposed to outpatient) than whites. The completion rate disparity between African Americans and whites could be cut by one-fifth if African Americans were to receive residential treatment at the same rate as whites do. These findings suggest some of the contributors to a significant alcohol treatment disparity between whites and minorities in Los Angeles County and begin to indicate what might be done about it. However, there is much about the disparity—such as the roles of patient economic resources and treatment facility neighborhoods—that is not yet understood, and it is uncertain whether these factors are the same in other locations.

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Influence of epipregnanolone on the modulation of rapid tolerance to ethanol by neurosteroids.
Rev. Bras. Psiquiatr., Dec 2007, vol.29, no.4, p.337-345.

The objective of the present study was to investigate the effect of epipregnanolone on the influence of neurosteroids on the development of rapid tolerance to the motor impairing and hypothermic effects of ethanol.

Pretreatment with epipregnanolone (0.10-0.30 mg/kg) significantly blocked the development of tolerance to the motor impairing and hypothermic effects induced by ethanol in mice. Considering tolerance to ethanol-induced motor impairment, epipregnanolone (0.15 mg/kg) reversed the stimulatory action of dehydroepiandrosterone sulfate (0.15 mg/kg), but did not affect the actions of pregnenolone sulfate (0.08 mg/kg). Moreover, epipregnanolone prevented the inhibitory action of allotetrahydrodeoxycorticosterone (0.10 mg/kg). In relation to ethanol-induced hypothermia, the results showed that pretreatment with epipregnanolone (0.30 mg/kg) significantly prevented the stimulatory action of dehydroepiandrosterone sulfate and pregnenolone sulfate, as well as the inhibitory action of allotetrahydrodeoxicorticosterone (0.20 mg/kg), on tolerance to this effect.

The results suggest a differential interaction between neurosteroids that might modulate the development of rapid tolerance to ethanol.

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Welcome to the latest
'What's new on the Alcohol Information Scotland website'

New on the site
Latest publications include:
Drinking places: Where people drink and why		Joseph Rowntree Foundation
	Criminal Justice Series: Homicide in Scotland, 2006-07		Scottish Government
	Alcohol-related Hospital Statistics		ISD Scotland
	Highlights from latest media comment
	Date	Publication	Publisher
	16th January	Helensburgh disco to breathalyse kids aged thirteen	Evening Times
	16th January	More beds to care for increase in brain-damaged drinkers	Evening News
	15th January	'Lothians and Edinburgh Abstinence Programme (LEAP)	The Scotsman
	14th January	Fall in festive drink-drive figures	Various Sources
	12th January	Lothian Police target underage drinkers on trains	Evening News
	9th January	Ban on drinking in public	Scottish Government
	8th January	Study finds less disease amongst moderate drinkers	The Guardian
	7th January	Police want tougher sentences for 'hard-core' drink drivers	Evening News
	Forthcoming Events
	A list of forthcoming workshops, training courses, seminars and conferences ___________________________________________________________________________

Frequency, course and corelates of alcohol use from adolescence to young adulthood in a Swiss community survey
BMC Psychiatry 2008, 8:5 17 January 2008

Few studies have analyzed the frequency of alcohol use across time from adolescence to young adulthood and its outcome in young adulthood.

A Swiss longitudinal multilevel assessment project using various measures of psychopathology and psychosocial variables allowed for the study of the frequency and correlates of alcohol use so that this developmental trajectory may be better understood.

The increase of alcohol use from early adolescence to young adulthood showed only a few sex-specific differences in terms of the amount of alcohol consumption and the motives to drink. In late adolescence and young adulthood, males had a higher amount of alcohol consumption and were more frequently looking for drunkenness and feeling high. Males also experienced more negative consequences of alcohol use.

A subgroup of heavy or problem drinkers showed a large range of emotional and behavioural problems and further indicators of impaired psychosocial functioning both in late adolescence and young adulthood.

This Swiss community survey documents that alcohol use is problematic in a sizeable proportion of youth and goes hand in hand with a large number of psychosocial problems.

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Nine-Year Psychiatric Trajectories and Substance Use Outcomes
Evaluation Review, Vol. 32, No. 1, 39-58 (2008)


This study identifies longitudinal psychiatric trajectories of 934 adult individuals entering chemical dependency treatment in a private, managed care health plan and examines the relationship of these trajectories with substance use (SU) outcomes.

The authors apply a group-based modeling approach to identify trajectory groups based on repeated measures of psychiatric severity for 9 years and identify four distinct groups.

Results of multivariate logistic generalized estimating equation models find an association between psychiatric trajectories and long-term SU. Older cohorts and life course measures of marital status and employment status as individuals changed over time are related to drug and some alcohol outcomes.

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Request Reprint E-Mail: Felicia.W.Chi@kp.org
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The Interaction of Co-Occurring Mental Disorders and Recovery Management Checkups on Substance Abuse Treatment Participation and Recovery
Evaluation Review, Vol. 32, No. 1, 7-38 (2008)


This article examines the effectiveness of quarterly Recovery Management Checkups (RMCs) for people with substance disorders by level of co-occurring mental disorders (34% none, 27% internalizing disorders, and 39% internalizing and externalizing) across two randomized experiments with 92% to 97% follow-up.

It is effective in linking participants in need to treatment, with equal or better outcomes among those with more mental disorders.

The data support the utility of monitoring and re-intervention for clients with co-occurring disorders.

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Request Reprint E-Mail: brian_rush@camh.net
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Different Effects of Fathers' Drinking Problems on Drinking Behaviors, Depression, and Anxiety among Korean University Students by Gender.
J Korean Acad Fam Med. 2007 Dec;28(12):902-908. Korean.

Drinking problem is known to affect not only patients but also their offsprings. This study purposed to examine the drinking behaviors and emotional aspects of university students whose fathers have drinking problems.

The male students whose fathers have drinking problems showed higher rate of binge drinking , heavy drinking , and harmful and hazardous drinking than the male students whose fathers do not have drinking problems. The female students whose fathers have drinking problems showed higher rate of depression than the female students whose fathers do not have drinking problems.

The results suggest that primary care physicians in a university setting need to evaluate and counsel drinking problems in male students, and emotional aspects in female students whose fathers have drinking problems.

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Request Reprint E-Mail: jskim@cnuh.co.kr ___________________________________________________________________

FOR DEBATE - Asking the right questions in the right way: the need for a shift in research on psychological treatments for addiction
Addiction (OnlineEarly Articles) 09 Jan 2008

To identify possible reasons for the disappointingly negative results of methodologically rigorous controlled trials of psychological treatments in the addictions field.

Treatment research has been asking the wrong questions in the wrong way. Three necessary shifts in ways of conducting research are proposed: (i) the field should stop studying named techniques and focus instead on change processes; (ii) change processes should be studied within the broader, longer-acting systems of which treatment is part; and (iii) science in the field should be brought up to date by acknowledging a variety of sources of useful knowledge.

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Request Reprint E-Mail: j.f.orford@bham.ac.uk
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Substance misuse among older adults: a neglected but treatable problem
Addiction (OnlineEarly Articles) 17 January 2008

Substance misuse is generally thought of as a problem of young people, but such problems have no age limits. . . . . . .

Older people with substance misuse problems should have access to appropriate and effective health-care services and they should be treated with dignity and sensitivity. Once identified, older adults' substance misuse problems can be treated effectively, and these individuals can recover and maintain an improved quality of life. To achieve this goal, health-care providers may need specific training to learn how to recognize and address these problems among older adults.

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FOR DEBATE - On treatment mechanisms—what can we learn from the COMBINE study?
Addiction (OnlineEarly Articles) 9 January 2008

To discuss the results of combined pharmacotherapies and behavioural interventions for alcohol dependence as presented by the COMBINE study.

Although the main hypothesis in the COMBINE study was to determine if improvements in treatment outcome can be achieved by combining pharmacotherapy and behavioural interventions, the lack of support for this idea in the results of the study is merely mentioned in passing, but not really discussed. Instead, the COMBINE study group claims that the results of their study constitute support for the use of naltrexone in primary care settings. However, the empirical basis for this recommendation appears somewhat weak.

Furthermore, the COMBINE study group's discussions of the results could have benefited from a discussion of the treatment mechanisms that are supposed to have generated the improvement in the participants' drinking practices: what importance should we attribute to common mechanisms that are embedded in the treatment context, and what weight should we ascribe to the pharmacological interventions and the specific behavioural intervention?

In the context of other major studies within the alcohol field, such as Project MATCH and the UK Alcohol Treatment Trial (UKATT) study, and contemporary psychotherapy research, it seems reasonable to regard the main results from the COMBINE as supportive of a need to change the focus of future addiction treatment research.

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Request Reprint E-Mail: anders.bergmark@socarb.su.se

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The NIAAA Alcohol Alert
No. 72: Alcohol Metabolism: An Update (2007)

This Alcohol Alert describes the basic process involved in the breakdown of alcohol, including how toxic byproducts of alcohol metabolism may lead to problems such as alcoholic liver disease, cancer, and pancreatitis. This Alert also describes populations who may be at particular risk for problems resulting from alcohol metabolism as well as people who may be genetically “protected” from these adverse effects.

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The combined influence of leisure-time physical activity and weekly alcohol intake on fatal ischaemic heart disease and all-cause mortality
European Heart Journal Advance Access published online on January 9, 2008

To determine the combined influence of leisure-time physical activity and weekly alcohol intake on the risk of subsequent fatal ischaemic heart disease (IHD) and all-cause mortality.

Within both genders, being physically active was associated with lower hazard ratios (HR) of both fatal IHD and all-cause mortality than being physically inactive.

Further, weekly alcohol intake was inversely associated with fatal IHD and had a U-shaped association with all-cause mortality. Within level of physical activity, non-drinkers had the highest HR of fatal IHD, whereas both non-drinkers and heavy drinkers had the highest HR of all-cause mortality.

Further, the physically inactive had the highest HR of both fatal IHD and all-cause mortality within each category of weekly alcohol intake. Thus, the HR of both fatal IHD and all-cause mortality were low among the physically active who had a moderate alcohol intake.

Leisure-time physical activity and a moderate weekly alcohol intake are both important to lower the risk of fatal IHD and all-cause mortality.

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The CRF-1 Receptor Antagonist, CP-154,526, Attenuates Stress-Induced Increases in Ethanol Consumption by BALB/cJ Mice
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 21 Dec 2007

Corticotropin-releasing factor (CRF) signaling modulates neurobiological responses to stress and ethanol, and may modulate observed increases in ethanol consumption following exposure to stressful events.

The current experiment was conducted to further characterize the role of CRF₁ receptor (CRF₁R) signaling in stress-induced increases in ethanol consumption in BALB/cJ and C57BL/6N mice.

Importantly, BALB/cJ mice pretreated with the CRF₁R antagonist showed blunted stress-induced increases in ethanol intake, and the CRF₁R antagonist did not influence the ethanol drinking of non-stressed mice.

The present results provide evidence that CRF₁R signaling modulates the delayed increase of ethanol consumption stemming from repeated exposure to a stressful event in BALB/cJ mice.

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Request Reprint E-Mail: thiele@unc.edu

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Parenting Mechanisms in Links Between Parents’ and Adolescents’ Alcohol Use Behaviors
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles)\ 21 Dec 2007

Adolescence has been identified as a critical period with regard to the initiation and early escalation of alcohol use. Moreover, research on familial risk and protective processes provides independent support for multiple domains of parental influence on adolescent drinking; including parents’ own drinking behaviors, as well as the practices they employ to socialize their children. Despite this prevalence of findings, whether and how these distinct associations are related to one another is still not entirely clear.

This study demonstrates that parenting is an important mediator of the association between parental and adolescent drinking practices. An important area for future research will be to study how adolescents can avoid alcohol-related problems despite being reared within a risk laden parenting environment and/or having parents who drink frequently.

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Request Reprint E-Mail: slatendresse@vcu.edu

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Ethanol Increases Fetal Human Neurosphere Size and Alters Adhesion Molecule Gene Expression
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 20 Dec 2007

Ethanol (ETOH) consumption by pregnant women can result in Fetal Alcohol Spectrum Disorder (FASD). To date, the cellular targets and mechanisms responsible for FASD are not fully characterized. Our aim was to determine if ETOH can affect fetal human brain-derived neural progenitor cells (NPC).

ETOH had no effect on NPC apoptosis but, resulted in more rapid coalescence and increased volume of neurospheres. Additionally, the expression of genes associated with cell adhesion was significantly altered. ETOH induced changes in NPC surface adhesion interactions may underlie aspects of neurodevelopmental abnormalities in FASD.

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Request Reprint E-Mail: svangipuram@med.wayne.edu

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The Reinforcing Properties of Salsolinol in the Ventral Tegmental Area: Evidence for Regional Heterogeneity and the Involvement of Serotonin and Dopamine
Alcoholism: Clinical and Experimental Research (OnlineEarly Articles) 21 Dec 2007

Salsolinol (SAL), the condensation product of acetaldehyde and dopamine, may be a factor contributing to alcohol abuse. Previous research indicated that both ethanol and acetaldehyde are self-administered into the posterior ventral tegmental area (VTA).

The current study examined SAL self-infusions into the VTA, and determined the involvement of dopamine neurons and 5-HT₃ receptors in this process.

SAL produces reinforcing effects in the posterior VTA of Wistar rats, and these effects are mediated by activation of DA neurons and local 5-HT₃ receptors.

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Request Reprint E-Mail: zrodd@iupui.edu
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Characteristics of Grandmothers who have Grandchildren with Fetal Alcohol Syndrome or Incomplete Fetal Alcohol Syndrome
Maternal and Child Health Journal, Online First, 15 January 2008

Characteristics of Northern Plains American Indian maternal grandmothers who had grandchildren with fetal alcohol syndrome (FAS) or incomplete FAS are described to more effectively prevent fetal FAS and alcohol use during pregnancy.

Study 1 had 27 maternal grandmothers who had grandchildren with FAS and Study 2 had 18 grandmothers with grandchildren who had incomplete FAS (cases) which were compared with 119 maternal grandmothers who had grandchildren without FAS (controls). The grandchildren were born between 1981 and 1993 on the Northern Plains. Medical records were manually reviewed for each case and control grandmother. Data were analyzed using Mantel–Haenszel chi square.

Study 1 case grandmothers were more likely to experience medical problems (70.4%) including trauma (48.1%) and injuries (51.9%) than the controls. Most of the Study 1 and 2 case grandmothers (92.6% and 77.8%, respectively) had alcohol use documented in their medical records compared to less than half of the control grandmothers. Seven (15.6%) of the case grandmothers had more than one grandchild in either Study 1 or Study 2.

Maternal grandmothers who had grandchildren with FAS had significantly higher rates of alcohol use and alcohol-related medical problems than control grandmothers.

Antenatal care providers should screen pregnant women for alcohol use at their first visit. The provider needs to ask the women who are using alcohol about their mothers’ use of alcohol to provide appropriate care and counseling for the women and prevent FAS.

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Request Reprint E-Mail: kvig6@aol.com
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Memory patterns of acquisition and retention of verbal and nonverbal information in children with fetal alcohol spectrum disorders
Can J Clin Pharmacol Vol 15(1) Winter 2008:e44-e56; January 9, 2008

Previous research indicates that children with FASD have both memory and learning deficits. However, there is no consensus about whether the deficits identified from a pattern of impairment, and whether this pattern is consistent with the current theories regarding the organization of memory. Thus, the goal of this study was to further explore memory functions and expose possible patterns that may exist in children with FASD.

A significant difference between types of verbal memory in the FASD sample was identified. Specifically, recall of word pairs was found to be more impaired than that for stories. In addition to this, recall of immediate word pairs was significantly more impaired than that for delayed word pairs, implying the presence of encoding deficits in this area.

Children and adolescents with FASD displayed specific types of verbal memory deficits and these deficits were greater for immediate rather than delayed memory. These data are consistent with previous studies that describe deficits in immediate memory, and suggest that deficits in delayed memory are better accounted for by encoding deficits. Furthermore, their greatest difficulty arose with those items in which the phonological loop was required, which would have facilitated learning though internal recitation and adequate phonological storage.

Further research into these distinctions in memory is warranted, as is exploration into educational techniques that could account for delayed encoding in children with FASD.

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Fetal alcohol syndrome related knowledge assessment and comparison in New Jersey health professional groups
Can J Clin Pharmacol Vol 15(1) Winter 2008:e57-e65; January 9, 2008

There is a need to educate health professionals in regard to Fetal Alcohol Syndrome and Fetal Alcohol Spectrum Disorders across many health and allied health fields.

Conduct evaluations of educational programs designed to assess knowledge, attitudes and beliefs in relation to Fetal Alcohol Spectrum Disorders (FASD) among health and allied health professionals in the northeastern United States.

FASD related educational efforts were carried out and evaluated in New Jersey for various health-related professional groups over a four-month period using a common set of materials. Pre and post-test evaluation comprised 20 questions on FASD recognition, diagnosis, treatment, and prevention. Groups surveyed included nurses, social workers, counselors, therapists, clinicians and allied health professionals comprising physician assistants, dieticians, physical therapists, occupational therapists.

Results showed that a majority of health care professionals in New Jersey possess basic knowledge related to FASD and the effects of alcohol on a child in utero. They also had significant awareness of the importance of early diagnosis and the importance of reducing secondary disabilities. The study did however reveal areas for improvement in some professional groups.

FASD is the most important preventable cause of mental retardation. Health professionals attending workshops typically had a good basic understanding of FASD, though with some weaknesses specific to their discipline. Educational efforts in regard to FASD should be sensitive to the various health professionals engaged in preventing, diagnosing and treating FASD.

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Increased MCP-1 and microglia in various regions of the human alcoholic brain
Experimental Neurology, Article in Press, Corrected Proof 3 December 2007


Cytokines and microglia have been implicated in anxiety, depression, neurodegeneration as well as the regulation of alcohol drinking and other consumatory behaviors, all of which are associated with alcoholism. Studies using animal models of alcoholism suggest that microglia and proinflammatory cytokines contribute to alcoholic pathologies

Alcoholics were found to have brain region-specific increases in microglial markers. In cingulate cortex, both Iba-1 and GluT₅ were increased in alcoholic brains relative to controls. Alternatively, no detectable change was found in amygdala nuclei. In VTA and midbrain, only GluT₅, but not Iba-1 was increased in alcoholic brains.

These data suggest that the enhanced expression of MCP-1 and microglia activities in alcoholic brains could contribute to ethanol-induced pathogenesis.

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Request Reprint E-Mail: ftcrews@med.unc.edu _____________________________________________________________________

Primary Care Intervention to Reduce Alcohol Misuse Ranking Its Health Impact and Cost Effectiveness
American Journal of Preventive Medicine, Volume 34, Issue 2, February 2008, Pages 143-152.e3

The U.S. Preventive Services Task Force (USPSTF) has recommended screening and behavioral counseling interventions in primary care to reduce alcohol misuse. This study was designed to develop a standardized rating for the clinically preventable burden and cost effectiveness of complying with that recommendation that would allow comparisons across many recommended services.

A systematic review of the literature from 1992 through 2004 to identify relevant randomized controlled trials and cost-effectiveness studies was completed in 2005. Clinically preventable burden (CPB) was calculated as the product of effectiveness times the alcohol-attributable fraction of both mortality and morbidity (measured in quality-adjusted life years or QALYs), for all relevant conditions. Cost effectiveness from both the societal perspective and the health-system perspective was estimated. These analyses were completed in 2006.

The calculated CPB was 176,000 QALYs saved over the lifetime of a birth cohort of 4,000,000, with a range in sensitivity analysis from −43% to +94% (primarily due to variation in estimates of effectiveness). Screening and brief counseling was cost-saving from the societal perspective and had a cost-effectiveness ratio of $1755/QALY saved from the health-system perspective. Sensitivity analysis indicates that from both perspectives the service is very cost effective and may be cost saving.

These results make alcohol screening and counseling one of the highest-ranking preventive services among the 25 effective services evaluated using standardized methods. Since current levels of delivery are the lowest of comparably ranked services, this service deserves special attention by clinicians and care delivery systems.

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Request Reprint E-Mail: leif.i.solberg@healthpartners.com
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