ICAP Reviews 4. Conflicting Interests, but Not Necessarily Conflicts of Interest

The question at the heart of this issue of ICAP Reviews is, “What actual, potential or perceived conflicts of interest may prevent stakeholders from playing a full role in alcohol policy development?”

Although the emphasis of public debate around this issue tends to focus on the role of the private sector, the question could equally apply to nongovernmental organizations and other civil society stakeholders.

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News Release - GENERAL ASSEMBLY ADOPTS RESOLUTION ON EASING GLOBAL ROAD SAFETY CRISIS,

Adopting a resolution aimed at alleviating the global road safety crisis, the General Assembly this morning welcomed the Russian Federation’s offer to host and provide financial support for the first global high-level conference on road safety, to be held next year.

Also by that text, which it adopted without a vote, the Assembly encouraged States to strengthen their commitments to road safety by observing the annual World Day of Remembrance for Road Traffic Victims in December, organizing global road safety weeks and encouraging fleet-owning organizations in both the private and public sectors to develop and implement policies and practices that would reduce road-crash risks. . . . . .

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Global Information System on Alcohol and Health (GISAH)

Given the significance of alcohol consumption to health, the World Health Organization (WHO) has prioritized continuous monitoring of alcohol consumption, alcohol-related harm and policy responses in its Member States over the last years.

Since 1997, the Management of Substance Abuse team in the WHO Department of Mental Health and Substance Abuse has been building the Global Alcohol Database and later the Global Information System on Alcohol and Health, providing a reference source of information for global epidemiological surveillance of alcohol use, alcohol-related problems and alcohol policies, based on passive epidemiological surveillance, and by gathering published and fugitive data and information about key aspects of the alcohol situation in WHO Member States.

The Global Information System on Alcohol and Health is overseen by a Steering Committee comprised of representatives from the WHO Department of Mental Health and Substance Abuse, the Centre for Addiction and Mental Health (Canada) and the Research Institute for Public Health and Addictions (Switzerland). The financial support from the Valencian Autonomous Government, Spain is gratefully acknowledged.

Indicators

For the Global Information System on Alcohol and Health a set of indicators was chosen to assess the most important aspects of the alcohol situation in WHO Member States as they relate to public health. The indicators are grouped into broad categories. Under each broad category there are topics and a number of sub-topics. The broad categories are as follows:

1. Production and Availability 2. Levels of Consumption 3. Patterns of Consumption 4. Harms and Consequences 5. Economic Aspects 6. Alcohol Control Policies 7. Prevention and Treatment 8. Comparative Risk Assessment

Regional information systems

The Global Information System on Alcohol and Health also serves as the global data repository for WHO regional information systems on alcohol and health. These can be accessed through the WHO regional offices websites, as follows:

- Regional Office for the Americas: Alcohol - Regional Office for Europe: Alcohol and Drugs - Regional Office for South-East Asia: Alcohol and Substance Abuse - Regional Office for the Western Pacific: Substance Abuse

Global Status Report on Alcohol and Health

The WHO global status reports on alcohol and health are largely based on information from GISAH. Previous reports are the following:

Global Status Report on Alcohol 2004 Country Profiles: Alcohol 2004 Global Status Report: Alcohol Policy 2004 Country Profiles: Alcohol Policy 2004 Global Status Report: Alcohol and Young People 2001 Global Status Report on Alcohol 1999 ____________________________________________

A Novel Role for Glyceraldehyde-3-Phosphate Dehydrogenase and Monoamine Oxidase B Cascade in Ethanol-Induced Cellular Damage

Alcoholism is a major psychiatric condition at least partly associated with ethanol (EtOH)-induced cell damage. Although brain cell loss has been reported in subjects with alcoholism, the molecular mechanism is unclear. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and monoamine oxidase B (MAO B) reportedly play a role in cellular dysfunction under stressful conditions and might contribute to EtOH-induced cell damage.

Ethanol significantly increases levels of GAPDH, especially nuclear GAPDH, and MAO B in neuronal cells as well as in human and rat brains. Nuclear GAPDH interacts with the transcriptional activator, transforming growth factor-β-inducible early gene 2 (TIEG2), and augments TIEG2-mediated MAO B transactivation, which results in cell damage in neuronal cells exposed to EtOH. Knockdown expression of GAPDH or treatment with MAO B inhibitors selegiline (deprenyl) and rasagiline (Azilect) can block this cascade.

Ethanol-elicited nuclear GAPDH augments TIEG2-mediated MAO B, which might play a role in brain damage in subjects with alcoholism. Compounds that block this cascade are potential candidates for therapeutic strategies.

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Request Reprint E-Mail: xou@psychiatry.umsmed.edu

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The Nociceptin/Orphanin FQ System as a Target for Treating Alcoholism

Nociceptin (known also as orphanin FQ) is the most recently discovered member of the endogenous opioid peptide family, albeit nearly 15 years ago. Nociceptin renders or influences many behavioral, psychological and neurobiological processes, including memory, anxiety, stress and reward.

Since its discovery, results of a steady stream of studies have suggested that endogenous nociceptin might be involved in responses to addictive drugs, and that targeting the nociceptin system may be beneficial in treating addictions.

The current review summarizes and critically appraises those studies, particularly those that point to an application in treating alcoholism.

Overall, most studies suggest that the endogenous nociceptin system has a physiological role in mediating or regulating behavioral responses to alcohol, and that activating nociceptin receptors suppresses ongoing alcohol consumption or reinstatement of responding for alcohol.

These findings encourage the development of therapies targeted at the nociceptin system for the treatment of alcoholism in humans, though a minor number of studies showing continuous activation of the nociceptin receptor can produce increased, rather than reduced, alcohol consumption emphasize the necessity of further investigation.

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Request Reprint E-Mail: nmurphy@ucla.edu
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A genome-wide association study of alcohol dependence

Excessive alcohol consumption is one of the leading causes of preventable death in the United States. Approximately 14% of those who use alcohol meet criteria during their lifetime for alcohol dependence, which is characterized by tolerance, withdrawal, inability to stop drinking, and continued drinking despite serious psychological or physiological problems.

We explored genetic influences on alcohol dependence among 1,897 European-American and African-American subjects with alcohol dependence compared with 1,932 unrelated, alcohol-exposed, nondependent controls.

Further dissection of the alcoholism phenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence.

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Distinct Effects of Protracted Withdrawal on Affect, Craving, Selective Attention and Executive Functions among Alcohol-Dependent Patients

The present study examined the effects of protracted alcohol withdrawal on affectivity, craving, selective attention and executive functions (EFs) in alcohol-dependent patients.

Alcohol-dependent patients' abilities to focus their attention on relevant information, to switch from one pattern to another, to inhibit irrelevant information and to make advantageous choices were lower than those of control participants during both times of a withdrawal cure. No effect of time emerged from analyses for selective attention and EF deficits.

Conversely, significant differences between T1 and T2 were observed for craving and affect scores indicating a weakening of alcohol craving and negative affect as well as an improvement of positive affect among patients from onset to the end of cure.

Control functions of the Supervisory Attentional System (Norman and Shallice, 1986) were impaired and did not improve during a 3-week withdrawal cure, whereas alcohol craving and negative state affectivity significantly improved in parallel during this period. Implications for understanding the clinical processes of withdrawal are discussed.

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Request Reprint E-Mail: Mariana.Cordovil@uclouvain.be
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Press Release - Drinkaware-funded project shows youngsters how to ‘side step’ alcohol misuse

'
Side Stepping Alcohol Misuse’, an alcohol awareness project run by London Active Communities and Premier Rugby, is due to kick off across the country this month after receiving £100,000 funding from the charity, Drinkaware. . . . . .

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Statistical modeling of volume of alcohol exposure for epidemiological studies of population health: the US example

Alcohol consumption is a major risk factor in the global burden of disease, with overall volume of exposure as the principal underlying dimension. Two main sources of data on volume of alcohol exposure are available: surveys and per capita consumption derived from routine statistics such as taxation. As both sources have significant problems, this paper presents an approach that triangulates information from both sources into disaggregated estimates in line with the overall level of per capita consumption.

The triangulation of survey data with aggregated per capita consumption data proved feasible and allowed for modeling of alcohol exposure disaggregated by sex, age, and ethnicity. These models can be used in combination with risk relations for burden of disease calculations. Sensitivity analyses showed that the gamma distribution chosen yielded very similar results in terms of fit and alcohol-attributable mortality as the other tested distributions.

Modeling alcohol consumption via the gamma distribution was feasible. To further refine this approach, research should focus on the main assumptions underlying the approach to explore differences between volume estimates derived from surveys and per capita consumption figures.

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Medical marijuana users in substance abuse treatment

The rise of authorized marijuana use in the U.S. means that many individuals are using cannabis as they concurrently engage in other forms of treatment, such as substance abuse counseling and psychotherapy. Clinical and legal decisions may be influenced by findings that suggest marijuana use during treatment serves as an obstacle to treatment success, compromises treatment integrity, or increases the prevalence or severity of relapse.

In this paper, the author reviews the relationship between authorized marijuana use and substance abuse treatment utilizing data from a preliminary pilot study that, for the first time, uses a systematic methodology to collect data examining possible effects on treatment.

While the findings described here are preliminary and very limited due to the small sample size, the study demonstrates that questions about the relationship between medical marijuana use and involvement in drug treatment can be systematically evaluated. In this small sample, cannabis use did not seem to compromise substance abuse treatment amongst the medical marijuana using group, who (based on these preliminary data) fared equal to or better than non-medical marijuana users in several important outcome categories (e.g., treatment completion, criminal justice involvement, medical concerns).

This exploratory study suggests that medical marijuana is consistent with participation in other forms of drug treatment and may not adversely affect positive treatment outcomes.

These findings call for more extensive sampling in future research to allow for more rigorous research on the growing population of medical marijuana users and non-marijuana users who are engaged in substance abuse treatment.

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The Protective Effect of Bee Venom against Ethanol-Induced Hepatic Injury via Regulation of the Mitochondria-Related Apoptotic Pathway

Alcohol consumption increases apoptosis of hepatocytes. Death of hepatocytes is a characteristic feature of chronic liver disease for various causes.

Bee venom (Apis mellifera) has been traditionally used for the treatment of various chronic diseases, such as chronic inflammatory arthritis and chronic liver disease. However, the precise mechanism for bee venom in chronic liver disease is not still cleared.

To assess the effects of bee venom in chronic liver disease, we investigated the potential role of the bee venom in the ethanol-induced hepatocyte apoptosis.

Bee venom treatment inhibited the apoptotic cell morphology and increased the cell viability in ethanol-induced hepatocyte apoptosis. With ethanol treatment, bee venom-treated hepatocytes increased activity of Bcl-2 and Bcl-xL, reduced activity of Bax, Caspase and PARP.

In conclusion, bee venom treatment in ethanol-induced hepatocyte apoptosis occurred through the regulation of Bcl family with subsequent inactivation of the Caspase and PARP.

These results suggest that bee venom could be an effective agent to reduce ethanol-induced hepatocyte apoptosis.

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Request Reprint E-Mail: kkpark@cu.ac.kr
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The role of alcohol and smoking in pancreatitis

Chronic alcohol use has been linked to chronic pancreatitis for over a century, but it has not been until the last decade that the role of alcohol in chronic pancreatitis has been elucidated in animals and, only in recent years, in human populations.

Although a dose-dependent association between alcohol consumption and chronic pancreatitis may exist, a staistical association has been shown only with the consumption of ≥5 alcoholic drinks per day. Smoking also confers a strong, independent and dose-dependent risk of pancreatitis that may be additive or multiplicative when combined with alcohol.

Alcohol increases the risk of acute pancreatitis in several ways and, most importantly, changes the immune response to injury. Genetic factors are also important and further studies are needed to clarify the role of gene–environment interactions in pancreatitis.

In humans, aggressive interventional counseling against alcohol use may reduce the frequency of recurrent attacks of disease and smoking cessation may help to slow the progression of acute to chronic pancreatitis.

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Request Reprint E-Mail: whitcomb@pitt.edu
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Brief alcohol intervention—where to from here? Challenges remain for research and practice

Brief intervention (BI) is intended as an early intervention for non-treatment-seeking, non-alcohol-dependent, hazardous and harmful drinkers.

This text provides a brief summary of key BI research findings from the last three decades and discusses a number of knowledge gaps that need to be addressed.

Five areas are described: patient intervention efficacy and effectiveness; barriers to BI implementation by health professionals; individual-level factors that impact on BI implementation; organization-level factors that impact on BI implementation; and society-level factors that impact on BI implementation.

BI research has focused largely upon the individual patient and health professional levels, with the main focus upon primary health care research, and studies are lacking in other settings. However, research must, to a larger degree, take into account the organizational and wider context in which BI occurs, as well as interactionbetween factors at different levels, in order to advance the understanding of how wider implementation of BI can be achieved in various settings and how different population groups can be reached. It is also important to expand BI research beyond its current parameters to investigate more ambitious long-term educational programmes and new organizational models.

More widespread implementation of BI will require many different interventions (efforts, actions, initiatives, etc.) at different interlinked levels, from implementation interventions targeting individual health professionals’ knowledge, skills, attitudes and behaviours concerning alcohol issues, BI and behaviour change counselling to efforts at the organizational and societal levels that influence the conditions for delivering BI as part of routine health care.

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Categorizing US State Drinking Practices and Consumption Trends

US state alcohol consumption patterns and trends are examined in order to identify groups of states with similar drinking habits or cultures. Rates of heavy drinking and current abstention and per capita apparent consumption levels are used to categorize states.

Six state groupings were identified: North Central and New England with the highest consumption and heavy drinking levels; Middle Atlantic, Pacific and South Coast with moderate drinking levels; and Dry South with the lowest drinking levels.

Analyses of relationships between beer and spirits series for states within groups as compared to those in different groups failed to clearly indicate group cohesiveness.

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NIAAA Director's Report on Institute Activities to the 123rd Meeting of the National Advisory Council on Alcohol Abuse and Alcoholism - February 4, 20

A. Legislation, Budget, and Policy

B. Director's Activities

C. NIAAA Staff and Organization

D. Multi-Media Products from NIAAA

E. Outreach

F. News Media Interactions

G. What's Ahead

H. NIAAA Program Annoucement and Request for Application Information

I. NIAAA Research Programs

J. Scientific Meetings

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Verbal and Nonverbal Memory in Adults Prenatally Exposed to Alcohol

Neurocognitive effects of prenatal alcohol exposure in adulthood are not well documented. Questions persist regarding the extent to which there are specific, measurable effects beyond those associated with global ability deficits, whether individuals without the full fetal alcohol syndrome (FAS) demonstrate alcohol-related cognitive impairments, and whether observed memory effects are specific to a particular modality, i.e., verbal vs. visual/spatial domains.

Results indicated that Dysmorphic individuals were significantly less efficient in memory performance than Controls on all of the outcomes measured, but they did not differ from those in the Special Education contrast group. The nondysmorphic, alcohol-exposed group was intermediate in their performance, suggesting a continuum of effects of prenatal exposure. Evaluation of the encoding and retrieval aspects of memory performance indicated that learning rather than forgetting accounted for the deficits associated with prenatal alcohol exposure. Finally, no interaction was found between modality of presentation (verbal and nonverbal) and effects of alcohol exposure on memory performance.

These findings indicate that prenatal alcohol exposure is associated with persistent and specific effects on memory performance, and these problems result from less efficient encoding of information across both verbal and nonverbal modalities. Education and training efforts with this clinical group should take these characteristics into account.

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Request Reprint E-Mail: ccoles@emory.edu

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Chronic Alcohol Consumption Is Associated With an Increased Cytotoxic Profile of Circulating Lymphocytes That May Be Related With the Development of L

Apoptosis has recently emerged as a key component of acute and chronic liver diseases and it could be related to alcoholic liver disease.

In the present study, we attempted to analyze the cytotoxic profile of circulating lymphocytes in chronic alcoholic patients grouped according to ethanol intake status and presence of liver disease.

AWLD patients showed an expansion of both CD4+/CD8+ cytotoxic T cells and NK/T cells, in association with an enhanced cytolytic activity against K562 cells and a higher ability to induce in vitro expression of the pro-apoptotic protein APO2.7 in HepG2 cells. Conversely, ethanol intake in ALC patients was associated with decreased NK cell numbers, a reduced cytotoxic activity against K562 cells without significant changes in the expression of APO2.7, and a pro-fibrotic profile of cytokine secretion.

Overall, our results suggest that alcoholic patients display different phenotypical and functional changes in circulating PB cytotoxic lymphocytes according to the presence of alcoholic liver disease, which could be related to the development and progress of liver injury.

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Request Reprint E-Mail: laso@usal.es

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Comparing Structural Equation Models That Use Different Measures of the Level of Response to Alcohol

The two measures of a low level of response (LR) to alcohol, an alcohol challenge and the retrospective Self-Report of the Effects of Alcohol questionnaire (SRE), each identify individuals at high risk for heavy drinking and alcohol problems. These measures also perform similarly in identifying subjects with unique functional brain imaging characteristics.

However, few data are available regarding whether alcohol challenge-based and SRE-based LRs operate similarly in structural equation models (SEMs) that search for characteristics, which help to mediate how LR impacts alcohol outcomes.

Two hundred and ninety-four men from the San Diego Prospective Study were evaluated for their LR to alcohol using alcohol challenges at ∼age 20. At ∼age 35, the same subjects filled out the SRE regarding the number of drinks needed for effects 15 to 20 years earlier. The two different LR scores for these men were used in SEM analyses evaluating how LR relates to future heavy drinking and to drinking in peers (PEER), alcohol expectancies (EXPECT), and drinking to cope (COPE) as potential mediators of the LR to drinking pattern (ALCOUT) relationships.

While the 2 LR measures that were determined 15 years apart related to each other at a modest level (r = 0.17, p <>

Consistent with the >60% overlap in prediction of outcomes for the 2 LR measures, and with results from functional brain imaging, alcohol challenge- and SRE-based LR values operated similarly in SEM models in these men.

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Request Reprint E-Mail mschuckit@ucsd.edu

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Induction of Innate Immune Gene Expression Cascades in Brain Slice Cultures by Ethanol: Key Role of NF-κB and Proinflammatory Cytokines

Postmortem human alcoholic brain has increased expression of proinflammatory cytokines (He and Crews, 2007). Nuclear factor κB (NF-κB) is a transcription factor known to induce proinflammatory cytokine expression. Ethanol exposure increases NF-κB–DNA binding in rat brain (Crews et al., 2006) and in brain slice cultures in vitro (Zou and Crews, 2006).

Using hippocampal-entorhinal cortex (HEC) brain slice cultures, we explored the effect of ethanol on NF-κB–DNA binding, proinflammatory gene expression, and sensitivity to glutamate neurotoxicity. Ethanol treatment results in a progressive increase in NF-κB–DNA binding that includes large increases in NF-κB subunit p50 protein–DNA binding. The expression of NF-κB proinflammatory target genes progressively increased with time of ethanol treatment. Ethanol induces proinflammatory cytokines TNFα, MCP-1, and IL-1β, proinflammatory proteases TACE, and tissue plasminogen activator (tPA) as well as inducible nitric oxide synthase. Blockade of NF-κB by using NF-κB p65 siRNA and BHT reduces ethanol induction of proinflammatory genes. Neutralizing antibody to proinflammatory cytokine TNFα reduces ethanol induction of proinflammatory genes, suggesting cytokine propagation of proinflammatory gene induction. Furthermore, neutralizing antibodies to proinflammatory cytokines and protease tPA inhibitors blunt ethanol sensitization to glutamate neurotoxicity

These findings indicate that ethanol treatment increases NF-κB–DNA binding and proinflammatory gene expression in brain slices. Ethanol-induced innate immune proinflammatory gene induction alters neurotransmission and likely contributes to alcoholic neurodegeneration.

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Requst Reprint E-Mail: ftcrews@med.unc.edu
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Functional polymorphism of matrix metalloproteinase-9 (MMP-9) gene in alcohol dependence: Family and case control study

Matrix metalloproteinases (MMP) are extracellularly acting endopeptidases, whose substrates are extracellular matrix and adhesion proteins.

In the gene polymorphism studies MMP-9 has been suggested to be involved in the pathogenesis of heart disease, cancer, bipolar disorder, and schizophrenia. In animal models MMP-9 has been shown to play a key role in a variety of neuronal plasticity phenomena, including learning and memory as well as drug addiction.

We found a statistically significant preferential transmission of the T allele (known to produce higher gene transcriptional activity) from parents to alcoholics (59%, p = 0.046). In case-control study genotype TT and T alleles were significantly more frequent in the alcoholics than in the controls (OR = 2.6).

Our results suggest that the MMP-9 gene may play a role in the pathogenesis of alcohol dependence.

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Request Reprint E-Mail: samoj@sci.pam.szczecin.pl

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Prenatal alcohol exposure reduces the size of the forelimb representation in motor cortex in rat: an intracortical microstimulation (ICMS) mapping stu

Children with fetal alcohol spectrum disorder (FASD) often exhibit sensorimotor dysfunctions that include deficits in motor coordination and fine motor control. Although the underlying causes for these motor abnormalities are unknown, they likely involve interactions between sensory and motor systems.

Rodent animal models have been used to study the effects of prenatal alcohol exposure (PAE) on skilled reaching and on the development and organization of somatosensory barrel field cortex. To this end, PAE delayed the development of somatosensory cortex, reduced the size of whisker and forelimb representations in somatosensory barrel field cortex, and delayed acquisition time to learn a skilled reaching task. However, whether PAE also affects the motor cortex (MI) remains to be determined.

In the present study, we investigated the effect of PAE on the size of the forelimb representation in rat MI, thresholds for activation, and the overlap between motor and sensory cortical forelimb maps in sensorimotor cortex.

Pregnant Sprague–Dawley rats were assigned to alcohol (Alc), pair-fed (PF), and chow-fed (CF) groups on gestation day 1 (GD1). Rats in the Alc group (n=4) were chronically intubated daily with binge doses of alcohol (6g/kg body weight) from GD1 to GD20 that resulted in averaged blood alcohol levels measured on GD10 (mean=191.5±41.9mg/dL) and on GD17 (mean=247.0±72.4mg/dL). PF (n=2) and CF (n=3) groups of pregnant rats served as controls. The effect of PAE on the various dependent measures was obtained from multiple male offspring from each dam within treatment groups, and litter means were compared between the groups from alcohol-treated and control (Ct: CF and PF) dams. At approximately 8 weeks of age, rats were anesthetized with ketamine/xylazine and the skull opened over sensorimotor cortex. A tungsten microelectrode was then inserted into the depths of layer V and intracortical microstimulation was used to deliver trains of pulses to evoke muscle contractions and/or movements; maximum stimulating ≤100μA. When a motor response was observed, the threshold for movement was measured and the motor receptive field projected to the cortical surface to serve as representative point for that location. A motor map for the forelimb representation was generated by systematically stimulating at adjacent sites until current thresholds reached the maximum and/or motor responses were no longer evoked.

The major findings in this study were as follows: (1) PAE significantly reduced the area of the forelimb representation in the Alc offspring (6.01mm2, standard error of the mean=±0.278) compared with the Ct offspring (8.03mm2±0.586), (2) PAE did not significantly reduce the averaged threshold for activation of movements between groups, (3) PAE significantly reduced the percent overlap (Alc=31.1%, Ct=55.4%) between the forelimb representation in sensory and motor cortices, and (4) no significant differences were observed in averaged body weight, hemisphere weight, or age of animal between treatment groups.

These findings suggest that the effects of PAE are not restricted to somatosensory barrel field cortex but also involve the MI and may underlie deficits in motor control and sensorimotor integration observed among children with FASD

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Request Reprint E-Mail: rwaters@uthsc.edu
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Changes in gene expression in regions of the extended amygdala of alcohol-preferring rats after binge-like alcohol drinking

The objective of this study was to determine time-course changes in gene expression within two regions of the extended amygdala after binge-like alcohol drinking by alcohol-preferring (P) rats.

Adult male P rats were given 1-h access to 15 and 30% ethanol three times daily for 8 weeks. Rats (n = 10/time point for ethanol and n = 6/time point for water) were killed by decapitation 1, 6, and 24 h after the last drinking episode. RNA was prepared from individual micropunch samples of the nucleus accumbens shell (ACB-shell) and central nucleus of the amygdala (CeA); analyses were conducted with Affymetrix Rat Genome 230.2 GeneChips. Ethanol intakes were 1.5–2 g/kg for each of the three sessions.

There were no genes that were statistically different between the ethanol and water control groups at any individual time point.

Therefore, an overall effect, comparing the water control and ethanol groups, was determined.

In the ACB-shell and CeA, there were 276 and 402 probe sets for named genes, respectively, that differed between the two groups. There were 1.5–3.6-fold more genes with increased expression than with decreased expression in the ethanol-drinking group, with most differences between 1.1- and 1.2-fold.

Among the differences between the ethanol and water control groups were several significant biological processes categories that were in common between the two regions (e.g., synaptic transmission, neurite development); however, within these categories, there were few genes in common between the two regions.

Overall, the results indicate that binge-like alcohol drinking by P rats produces region-dependent changes in the expression of genes that could alter transcription, synaptic function, and neuronal plasticity in the ACB-shell and CeA; within each region, different mechanisms may underlie these alterations because there were few common ethanol-responsive genes between the ACB-shell and CeA.

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Request Reprint E-Mail: wmcbride@iupui.edu
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