GluN2B in corticostriatal circuits governs choice learning and choice shifting.

 

A choice that reliably produces a preferred outcome can be automated to liberate cognitive resources for other tasks. Should an outcome become less desirable, behavior must adapt in parallel or it becomes perseverative. Corticostriatal systems are known to mediate choice learning and flexibility, but the molecular mechanisms of these processes are not well understood.

We integrated mouse behavioral, immunocytochemical, in vivo electrophysiological, genetic and pharmacological approaches to study choice.

We found that the dorsal striatum (DS) was increasingly activated with choice learning, whereas reversal of learned choice engaged prefrontal regions. In vivo, DS neurons showed activity associated with reward anticipation and receipt that emerged with learning and relearning. Corticostriatal or striatal deletion of Grin2b (encoding the NMDA-type glutamate receptor subunit GluN2B) or DS-restricted GluN2B antagonism impaired choice learning, whereas cortical Grin2b deletion or OFC GluN2B antagonism impaired shifting.

Our convergent data demonstrate how corticostriatal GluN2B circuits govern the ability to learn and shift choice behavior.


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Request Reprint E-Mail:    Andrew.Holmes@nih.gov

Overcoming Addictions, a Web-Based Application, and SMART Recovery, an Online and In-Person Mutual Help Group for Problem Drinkers, Part 1: Three-Month Outcomes of a Randomized Controlled Trial

Overcoming Addictions (OA) is an abstinence-oriented, cognitive behavioral, Web application based on the program of SMART Recovery. SMART Recovery is an organization that has adapted empirically supported treatment strategies for use in a mutual help framework with in-person meetings, online meetings, a forum, and other resources.

To evaluate the effectiveness of OA and SMART Recovery (SR) with problem drinkers who were new to SMART Recovery. Our experimental hypotheses were: (1) all groups will reduce their drinking and alcohol/drug-related consequences at follow-up compared to their baseline levels, (2) the OA condition will reduce their drinking and alcohol/drug-related consequences more than the control group (SR), and (3) the OA+SR condition will reduce their drinking and alcohol/drug-related consequences more than the control group (SR only).

We recruited 189 heavy problem drinkers primarily through SMART Recovery’s website and in-person meetings throughout the United States. We randomly assigned participants to (1) OA alone, (2) OA+attend SMART Recovery (SR) meetings (OA+SR), or (3) attend SR only. Baseline and follow-ups were conducted via GoToMeeting sessions with a Research Assistant (RA) and the study participant. We interviewed significant others to corroborate the participant’s self-report. Primary outcome measures included percent days abstinent (PDA), mean drinks per drinking day (DDD), and alcohol/drug-related consequences.

The intent-to-treat analysis of the 3-month outcomes supported the first hypothesis but not the others. Participants in all groups significantly increased their percent days abstinent from 44% to 72% (P<.001), decreased their mean drinks per drinking day from 8.0 to 4.6 (P<.001), and decreased their alcohol/drug-related problems (P<.001). Actual use relationships were found for the OA groups, between SR online meetings and improvement in PDA (r=.261, P=.033). In addition in the OA groups, the number of total sessions of support (including SR & other meetings, counselor visits) was significantly related to PDA (r=.306, P=012) and amount of improvement in alcohol-related problems (r=.305, P=.012). In the SR only group, the number of face-to-face meetings was significantly related to all three dependent variables, and predicted increased PDA (r=.358, P=.003), fewer mean DDD (r=-.250, P=.039), and fewer alcohol-related problems (r=-.244, P=.045), as well as to the amount of improvement in all three of these variables. Six-month follow-ups have been completed, and the results are currently being analyzed.

These results support our first experimental hypothesis but not the second or third. All groups significantly increased their PDA and decreased both their mean DDD and their alcohol-related problems, which indicates that both interventions being investigated were equally effective in helping people recover from their problem drinking.



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NIH study identifies brain circuits involved in learning and decision making

Finding has implications for alcoholism and other patterns of addictive behavior

Research from the National Institutes of Health has identified neural circuits in mice that are involved in the ability to learn and alter behaviors. The findings help to explain the brain processes that govern choice and the ability to adapt behavior based on the end results.

Researchers think this might provide insight into patterns of compulsive behavior such as alcoholism and other addictions.

“Much remains to be understood about exactly how the brain strikes the balance between learning a behavioral response that is consistently rewarded, versus retaining the flexibility to switch to a new, better response,” said Kenneth R. Warren, Ph.D., acting director of the National Institute on Alcohol Abuse and Alcoholism. “These findings give new insight into the process and how it can go awry.”

The study, published online in Nature Neuroscience, indicates that specific circuits in the forebrain play a critical role in choice and adaptive learning.  > > > >  Read More

Critique 116: Effects of genetic factors on metabolism of alcohol — 10 July 2013

Forum Comments

This paper presents an excellent summary of the effects of genetically determined enzymes that affect the metabolism of alcohol; such factors relate strongly to both the rewarding and the aversive effects of alcohol. Of almost 100 genes that have been found to relate to alcohol metabolism, the two major ones appear to be alcohol dehydrogenase and aldehyde dehydrogenase. The authors describe the metabolism of alcohol into acetaldehyde by alcohol dehydrogenase, and then focus especially on the metabolism of acetaldehyde by aldehyde dehydrogenase-2.

Previous studies have shown that 20-40% of individuals of East Asian origin have a point mutation in the genes that code for high affinity aldehyde dehydrogenase-2; such people tend to show high levels of acetaldehyde and develop flushing, tachycardia, headache, nausea, and emesis from even small amounts of alcohol. Being very intolerant of alcohol, they are at very low risk of alcohol abuse. This mutation is much less common among European and North American populations.  > > > >   Read More

Readiness to change and brain damage in patients with chronic alcoholism

High motivation to change is a crucial triggering factor to patients’ engagement in clinical treatment.

This study investigates whether the low readiness to change observed in some alcoholic inpatients at treatment entry could, at least partially, be linked with macrostructural gray matter abnormalities in critical brain regions.

Participants comprised 31 alcoholic patients and 27 controls, who underwent 1.5-T magnetic resonance imaging. The Readiness to Change Questionnaire, designed to assess three stages of motivation to change (precontemplation, contemplation and action stages), was completed by all patients, who were then divided into “Action” (i.e. patients in action stage) and “PreAction” (i.e. patients in precontemplation or in contemplation stage) subgroups.

The PreAction subgroup, but not the Action subgroup, had gray matter volume deficits compared with controls. Unlike the patients in the Action subgroup, the PreAction patients had gray matter abnormalities in the cerebellum (Crus I), fusiform gyri and frontal cortex.

The low level of motivation to modify drinking behavior observed in some alcoholic patients at treatment entry may be related to macrostructural brain abnormalities in regions subtending cognitive, emotional and social abilities.

These brain volume deficits may result in impairment of critical abilities such as decision making, executive functions and social cognition skills. Those abilities may be needed to resolve ambivalence toward alcohol addiction and to apply “processes of change”, which are essential for activating the desire to change problematic behavior.


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Request Reprint E-Mail:     helene.beaunieux@unicaen.fr

Alcohol Consumption, Types of Alcohol, and Parkinson’s Disease

The epidemiologic evidence on alcohol consumption and Parkinson’s disease (PD) is equivocal. We prospectively examined total alcohol consumption and consumption of specific types of alcoholic beverage in relation to future risk of PD.

The study comprised 306,895 participants (180,235 male and 126,660 female) ages 50–71 years in 1995–1996 from the NIH-AARP Diet and Health Study. Consumption of alcoholic beverages in the past 12 months was assessed in 1995–1996. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were obtained from logistic regression models.

A total of 1,113 PD cases diagnosed between 2000 and 2006 were included in the analysis. Total alcohol consumption was not associated with PD. However, the association differed by types of alcoholic beverages. Compared with non-beer drinkers, the multivariate ORs for beer drinkers were 0.79 for less than 1 drink/day, 0.73 for 1–1.99 drinks/day, and 0.86  for greater or equal drinks/day. For liquor consumption, a monotonic increase in PD risk was suggested: ORs  were 1.06 .22 , and 1.35  for less than 1, 1–1.99, and ≥2 drinks/day, respectively. Additional analyses among exclusive drinkers of one specific type of alcoholic beverage supported the robustness of these findings. The results for wine consumption were less clear, although a borderline lower PD risk was observed when comparing wine drinkers of 1–1.99 drinks/day with none drinkers .

Our results suggest that beer and liquor consumption may have opposite associations with PD: low to moderate beer consumption with lower PD risk and greater liquor consumption with higher risk. These findings and potential underlying mechanisms warrant further investigations.


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Ectopic hippocampal neurogenesis in adolescent male rats following alcohol dependence

The adolescent hippocampus is highly vulnerable to alcohol-induced damage, which could contribute to their increased susceptibility to alcohol use disorder. Altered adult hippocampal neurogenesis represents one potential mechanism by which alcohol (ethanol) affects hippocampal function.

Based on the vulnerability of the adolescent hippocampus to alcohol-induced damage, and prior reports of long-term alcohol-induced effects on adult neurogenesis, we predicted adverse effects on adult neurogenesis in the adolescent brain following abstinence from alcohol dependence.

Thus, we examined neurogenesis in adolescent male rats during abstinence following a 4-day binge model of alcohol dependence.

Bromodeoxyuridine and Ki67 immunohistochemistry revealed a 2.2-fold increase in subgranular zone cell proliferation after 7 days of abstinence. Increased proliferation was followed by a 75% increase in doublecortin expression and a 56% increase in surviving bromodeoxyuridine-labeled cells 14 and 35 days post-ethanol exposure, respectively.

The majority of newborn cells in ethanol and control groups co-localized with NeuN, indicating a neuronal phenotype and therefore a 1.6-fold increase in hippocampal neurogenesis during abstinence.

Although these results mirror the magnitude of reactive
neurogenesis described in adult rat studies, ectopic bromodeoxyuridine and doublecortin positive cells were detected in the molecular layer and hilus of adolescent rats displaying severe withdrawal symptoms, an effect that has not been described in adults.

The presence of ectopic neuroblasts suggests that a potential defect exists in the functional incorporation of new neurons into the existing hippocampal circuitry for a subset of rats.

Age-related differences in functional incorporation could contribute to the increased vulnerability of the adolescent hippocampus to ethanol.



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Request Reprint E-Mail:     kim-nixon@uky.edu

Conservatives retreat over minimum price on alcohol

Theresa May, the Home Secretary, is expected to tell MPs that the Prime Minister’s personal pledges to restrict access to cheap alcohol will not be implemented.

Instead, ministers will seek to enforce a much more modest change, banning retailers from selling alcohol at very cheap prices in “loss-leader” deals.

The ban on selling alcohol below cost price will be presented as a way to tackle problem drinking.

Government insiders admit that the new plan represents a significant retreat from Mr Cameron’s promises, since it will have a smaller impact on prices and many sales will be unaffected.   > > > >   Read More

'On your doorstep; underage access to alcohol via home delivery services'

A new report by Alcohol Concern Cymru says children are often able to access alcohol via home delivery services. Earlier this year an online survey of nearly 1,000 people in Wales aged 14 and 17 years old explored their use of online supermarket grocery services and latenight and 24 hour alcohol home delivery services.   > > > >   Read More

Do men and women view drunkenness the same way?

At what point would you consider someone to be just "tipsy" as opposed to "hammered" on alcohol? The answer, it turns out, depends on whether you're a man or a woman.

In a study published online Wednesday in the journal Alcoholism: Clinical & Experimental Research, psychologists found that women were more likely to describe heavily intoxicated females as just "tipsy" or "buzzed," whereas men were more likely to describe other men as "wasted" or "hammered" even if they were just moderately drunk.

The difference in word choice -- which is probably influenced by a variety of social factors -- could carry significant consequences for women, particularly those of college age, according to lead study author Ash Levitt, a social psychologist at the Research Institute on Addictions at the University at Buffalo, SUNY.  > > > >   Read More

Combined impact of smoking and heavy alcohol use on cognitive decline in early old age: Whitehall II prospective cohort study

Identifying modifiable risk factors for  cognitive decline may inform prevention of dementia.

To examine the combined impact of cigarette smoking and heavy alcohol consumption on cognitive decline from midlife.

 

Prospective cohort study (Whitehall II cohort) with three clinical examinations in 1997/99, 2002/04 and 2007/09. Participants were 6473 adults (72% men), mean age 55.76 years (s.d. = 6.02) in 1997/99. Four cognitive tests, assessed three times over 10 years, combined into a global z-score (mean 0, s.d. = 1).

 

Age-related decline in the global cognitive score was faster in individuals who were smoking heavy drinkers than in non-smoking moderate alcohol drinkers (reference group). The interaction term (P = 0.04) suggested that the combined effects of smoking and alcohol consumption were greater than their individual effects. Adjusting for age, gender, education and chronic diseases, 10-year decline in global cognition was –0.42 z-scores (95% CI –0.45 to –0.39) for the reference group. In individuals who were heavy alcohol drinkers who also smoked the decline was –0.57 z-scores (95% CI –0.67 to –0.48); 36% faster than the reference group.

 

Individuals who were smokers who drank alcohol heavily had a 36% faster cognitive decline, equivalent to an age-effect of 2 extra years over 10-year follow-up, compared with individuals who were non-smoking moderate drinkers.

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Request Reprint E-Mail:     g.hagger-johnson@ucl.ac.uk

Availability of convenience stores and adolescent alcohol use in Taiwan: a multi-level analysis of national surveys

To examine the association between alcohol in school environments and adolescent alcohol use over the previous 6 months.

A multi-level logistic regression analysis was performed of cross-sectional surveys conducted in 2004, 2005 and 2006.

 

A total of 52 214 students aged 11–19 years from 387 middle or high schools were selected from a nationally representative, multi-stage, stratified probability sampling across Taiwan.
 

Information on socio-demographic features and substance use experiences was collected using self-administered questionnaires. The alcohol in the environment was measured using the availability of convenience stores surrounding the schools. Using geographical information systems, the weighted numbers of convenience stores within 1 km, a 12–15-minute walk, of a school were calculated. The schools were later categorized into three subgroups via the tertile of nearby convenience stores.

 

Considering the compositional characteristics, the availability of convenience stores was found to account for 1.5% of the school-level variance of youthful drinking. The odds ratios (95% confidence interval) of alcohol use over the previous 6 months among youth attending schools with medium and high availability were 1.04 (0.96–1.13) and 1.08 (1.00–1.17), respectively, with a P-value of 0.04 in the trend test.

 

The greater availability of convenience stores near a school is associated with an increased risk of alcohol use among adolescents over the previous 6 months.


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Request Reprint E-Mail:    wjchen@ntu.edu.tw

Preferences Regarding Treatment for Alcohol Problems

The aim of the study was to investigate preferences in the general population regarding type of treatment for alcohol problems and the preferred setting for delivery of treatment and reasons for not seeking treatment for alcohol problems.

Data were from a random, cross-sectional, interview survey of 9005 of the Swedish general population. Proportions of respondents preferring a certain treatment and source of treatment, and reasons suggested for why people do not seek treatment, were analysed in relation to number of standard drinks, employment status, education and income.

Most frequently endorsed forms of treatment were alcoholics anonymous or similar support groups and psychotherapy. More than 50% preferred psychiatric or addiction specialist treatment. Around 10% preferred primary health care and around 20% the occupational health services. About 5% preferred the social services. Respondents rated ‘feeling ashamed’ as the most important reason why people would not seek help for alcohol problems.

Large majorities of the respondents preferred treatment in the health care services and few in the social services. Internet-based treatment and pharmacological treatment attracted few respondents, the majority preferring more traditional forms of treatment. Alcohol treatment remains a stigmatized field, evidenced by shame being the most commonly reported reason for not seeking treatment.


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Request Reprint E-Mail:   sven.andreasson@ki.se

Gender Differences in Natural Language Factors of Subjective Intoxication in College Students: An Experimental Vignette Study

Examining the natural language college students use to describe various levels of intoxication can provide important insight into subjective perceptions of college alcohol use. Previous research (Levitt et al., Alcohol Clin Exp Res 2009; 33: 448) has shown that intoxication terms reflect moderate and heavy levels of intoxication and that self-use of these terms differs by gender among college students. However, it is still unknown whether these terms similarly apply to other individuals and, if so, whether similar gender differences exist.

 

To address these issues, the current study examined the application of intoxication terms to characters in experimentally manipulated vignettes of naturalistic drinking situations within a sample of university undergraduates (n = 145).

 

Findings supported and extended previous research by showing that other-directed applications of intoxication terms are similar to self-directed applications and depend on the gender of both the target and the user. Specifically, moderate intoxication terms were applied to and from women more than men, even when the character was heavily intoxicated, whereas heavy intoxication terms were applied to and from men more than women.

 

The findings suggest that gender differences in the application of intoxication terms are other-directed as well as self-directed and that intoxication language can inform gender-specific prevention and intervention efforts targeting problematic alcohol use among college students.


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Request Reprint E-Mail:     alevitt@ria.buffalo.edu

Adolescent Alcohol Use is Predicted by Childhood Temperament Factors Before Age 5, with Mediation Through Personality and Peers

Very few studies chart developmental pathways from early childhood to adolescent alcohol-related outcomes. We test whether measures of temperament collected from mothers at multiple assessments from 6 months through 5 years predict alcohol-related outcomes in mid-adolescence, the developmental pathways that mediate these effects, and whether there are gender differences in pathways of risk.

 

Structural models were fit to longitudinal data from the Avon Longitudinal Study of Parents and Children, an epidemiological sample of pregnant women with delivery dates between April 1991 and December 1992, with children followed longitudinally. Temperamental characteristics were assessed at 6 time points from 6 to 69 months of age. Alcohol use and problems were assessed at age 15.5. Analyses here utilize data from 6,504 boys and 6,143 girls.

 

Childhood temperament prior to age 5 predicted adolescent alcohol use and problems at age 15.5 years, even after controlling for socio-demographic factors and parental alcohol problems. In both boys and girls, 2 largely uncorrelated and distinct temperament styles—children who were rated as having consistent emotional and conduct difficulties through age 5, and children who were rated as consistently sociable through age 5—both showed elevated rates of alcohol problems at age 15.5, but via different mediational pathways. In both genders, the association between emotional and conduct difficulties and alcohol problems was mediated through reduced conscientiousness and lower emotional stability. The association between sociability and alcohol problems was mediated through increased extraversion and sensation-seeking for both genders. Boys also showed mediation for sociability and alcohol outcomes through friendship characteristics, and girls through lower conscientiousness and reduced emotional stability.

 

Our findings support multiple pathways to alcohol consumption and problems in adolescence. Some of these pathways are shared in boys and girls, while other risk factors are more salient in one gender or the other.


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Request Reprint E-Mail:     ddick@vcu.edu

A Preliminary Study of the Human Brain Response to Oral Sucrose and Its Association with Recent Drinking

A preference for sweet tastes has been repeatedly shown to be associated with alcohol preference in both animals and humans. In this study, we tested the extent to which recent drinking is related to blood oxygen level–dependent (BOLD) activation from an intensely sweet solution in orbitofrontal areas known to respond to primary rewards.

 

Sixteen right-handed, non-treatment-seeking, healthy volunteers (mean age: 26 years; 75% male) were recruited from the community. All underwent a taste test using a range of sucrose concentrations, as well as functional magnetic resonance imaging (fMRI) during pseudorandom, event-driven stimulation with water and a 0.83 M concentration of sucrose in water.

 

[Sucrose > water] provoked a significant BOLD activation in primary gustatory cortex and amygdala, as well as in the right ventral striatum and in bilateral orbitofrontal cortex. Drinks/drinking day correlated significantly with the activation as extracted from the left orbital area (r = 0.52, p = 0.04 after correcting for a bilateral comparison). Using stepwise multiple regression, the addition of rated sucrose liking accounted for significantly more variance in drinks/drinking day than did left orbital activation alone (multiple R = 0.79, p = 0.002).

 

Both the orbitofrontal response to an intensely sweet taste and rated liking of that taste accounted for significant variance in drinking behavior. The brain response to sweet tastes may be an important phenotype of alcoholism risk.


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Request Reprint E-Mail:    dkareken@iupui.edu

A longitudinal examination of adolescent response inhibition: neural differences before and after the initiation of heavy drinking

 

Response inhibition abnormalities contribute to several maladaptive behaviors commonly observed during adolescence, including heavy drinking.

 

The present study aimed to determine whether abnormalities in brain response during response

inhibition predate or follow adolescents’ transition into heavy drinking, which is pivotal in identifying the neural antecedents and consequences of adolescent alcohol use.

Longitudinal functional magnetic resonance imaging (fMRI) acquired during a response inhibition task was collected on adolescents before the onset of heavy drinking and then again on the same scanner approximately 3 years later. Adolescents who transitioned into heavy drinking (n = 20) were matched to continuously nondrinking adolescents (n = 20) on baseline and follow-up demographic and developmental variables.

 

During no-go relative to go trials, participants showed responses common to inhibitory circuitry: frontal (e.g., pre-supplementary motor area), temporal, and parietal regions. A repeated measures analysis of covariance revealed that adolescents who later transitioned into heavy drinking showed less fMRI response contrast at baseline than continuous nondrinkers in frontal, parietal, subcortical, and cerebellar regions (p < 0.01, clusters >756 μl), then increased activation after the onset of heavy drinking in frontal, parietal, and cerebellar areas.

 

Future heavy drinkers showed less activation of inhibitory circuitry before the onset of heavy drinking. After transitioning into heavy drinking, they showed more activation during response inhibition than nondrinking controls. These results contribute to the growing literature suggesting that neural vulnerabilities exist prior to the onset of substance use, and the initiation of heavy drinking may lead to additional alterations in brain functioning.

 

 

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Request Reprint E-Mail:     stapert@ucsd.edu

Global Actions: Commitments to Reduce Harmful Drinking. July 10, 2013

 

 

 

 

Global Actions in Focus

Collaborating with india’s ministry of health

Representatives from the International Spirits and Wines Association of India, Pernod Ricard India, and ICAP met with the Ministry of Health and Family Welfare Joint Secretary Mr. Anshu Prakash on June 6, 2013, to discuss the WHO’s guidelines to reduce the harmful use of beverage alcohol as a part of efforts to address noncommunicable diseases (NCDs).

The recently concluded World Health Assembly at Geneva reemphasized the need to increase the frequency of consultations with various stakeholders in order to address the growing concern of harmful drinking.

At the meeting, industry representatives outlined the projects and activities that have been undertaken, including those that focus on drink driving, binge drinking, underage drinking, training and eye camps for commercial truck drivers, and increasing awareness of responsible drinking. The representatives also highlighted the collaboration with the Health Ministry as they work on these issues.

Mr. Prakash welcomed the initiatives and activities taken by the beverage alcohol producers and agreed to work in conjunction with industry representatives in certain areas of concern. He also agreed that the primary objective should be to reduce the harmful use of beverage alcohol. It was suggested that there should be an emphasis on programs and campaigns that address the NCDs linked to unhealthy lifestyle choices, promote an increase in physical activity, and develop binge drinking education programs for youth.

Mr. Prakash also stressed the importance of the communication and advertising of responsible drinking at public events. He recommended that ICAP and industry representatives meet with other departments within the state governments, including the State Excise Department, to discuss drink driving campaigns and other projects. ICAP presented a booklet outlining several industry initiatives and future projects, including activities planned in partnership with Maharashtra/Andhra Pradesh and the Odisha Excise Department. Industry representatives also requested the creation of a committee of stakeholders to work with the Health Ministry and review projects to assess progress.

The meeting concluded with recommended steps to move forward:

1. Keep the Joint Secretary’s office informed of all industry initiatives through mail and personal interactions.

2. Rigorous action required to advance the formation of a committee of stakeholders working with the Health Ministry for concrete results.

3. Initiate discussions with a few state governments initially and implement some initiatives to showcase at the Health Ministry.

4. Design a new initiative based on the Joint Secretary’s recommendations and start discussion on its implementation.

Key Recent Milestones

· Worldwide: On July 4, 2013, ICAP announced that Anadolu Efes has become an ICAP Sponsor Company. ICAP President Marcus Grant welcomed the company and said, “Anadolu Efes joins us as we are working to develop an inclusive approach to addressing harmful drinking and put diverse resources to work on alcohol-related harms.”

What's Happening Next

· Colombia: Channel Research will be conducting their third site visit to Colombia for the Global Actions Drink Driving Initiative. The visit will take place from August 12 to 16, 2013, where the team will speak with various stakeholders.