The Role of Clock in Ethanol-Related Behaviors

 

Mice with a mutation in the Clock gene (ClockΔ19) exhibit increased preference for stimulant rewards and sucrose. They also have an increase in dopaminergic activity in the ventral tegmental area (VTA) and a general increase in glutamatergic tone that might underlie these behaviors. However, it is unclear if their phenotype would extend to a very different class of drug (ethanol), and if so, whether these systems might be involved in their response.

Continuous access voluntary ethanol intake was evaluated in ClockΔ19 mutants and wild-type (WT) mice. We found that ClockΔ19 mice exhibited significantly increased ethanol intake in a two-bottle choice paradigm. Interestingly, this effect was more robust in female mice. Moreover, chronic ethanol experience resulted in a long-lasting decrease in VTA Clock expression.

To determine the importance of VTA Clock expression in ethanol intake, we knocked down Clock expression in the VTA of WT mice via RNA interference.

We found that reducing Clock expression in the VTA resulted in significantly increased ethanol intake similar to the ClockΔ19 mice. Interestingly, we also discovered that ClockΔ19 mice exhibit significantly augmented responses to the sedative effects of ethanol and ketamine, but not pentobarbital. However, their drinking behavior was not affected by acamprosate, an FDA-approved drug for the treatment of alcoholism, suggesting that their increased glutamatergic tone might underlie the increased sensitivity to the sedative/hypnotic properties of ethanol but not the rewarding properties of ethanol.

Taken together, we have identified a significant role for Clock in the VTA as a negative regulator of ethanol intake and implicate the VTA dopamine system in this response.

 

 

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Government confirms no minimum pricing or multi-buy ban as health groups left reeling; Sheffield research assesses pricing impact on groups

 

The Government has confirmed it will not be introducing minimum unit pricing (MUP) in publishing its response to the alcohol strategy consultation. A proposed ban on multi-buy promotions has also been dropped, but previous plans for a 'below cost ban' have been resurrected, meaning alcohol will not be sold at lower than duty+VAT to 'stop the worst cases of heavy discounting'. 

 

In 2012 the Government's new alcohol strategy announced it would "introduce a new minimum unit price". However by 2013 it was stating it was listening to "powerful arguments on both sides" following consultation on a 45 pence MUP and other measures. Health bodies and other supporters, including Tory MP Sarah Wollaston, leveled that the Government had given in to industry lobbying.  > > > >  Read More

Preliminary Observation of Dynamic Changes in Alcohol Concentration in the Human Brain with Proton Magnetic Resonance Spectroscopy on a 3T MR Instrument.

 

Our purposes were to establish suitable conditions for proton magnetic resonance spectroscopy (MRS) to measure dynamic changes in alcohol concentration in the human brain, to evaluate these changes, and to compare the findings with data from analysis of breath vapor and blood samples.

We evaluated 4 healthy volunteers (mean age 26.5 years; 3 males, one female) with no neurological findings. All studies were performed with 3-tesla clinical equipment using an 8-channel head coil. We applied our modified single-voxel point-resolved spectroscopy (PRESS) sequence. Continuous measurements of MRS, breath vapor, and blood samples were conducted before and after the subjects drank alcohol with a light meal. The obtained spectra were quantified by LCModel Ver. 6.1, and the accuracy of the MRS measurements was estimated using the estimated standard deviation expressed in percentage (%SD) as a criterion.

Alcohol peaks after drinking were clearly detected at 1.2 ppm for all durations of measurement. Good correlations between breath vapor or blood sample and MRS were found by sub-minute MRS measurement. The continuous measurement showed time-dependent changes in alcohol in the brain and various patterns that differed among subjects.

The clinical 3T equipment enables direct evaluation of sub-minute changes in alcohol metabolism in the human brain.


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Request Reprint E-Mail:     sakama@medsci.tokushima-u.ac.jp.

Alcohol-related mortality in deprived UK cities: worrying trends in young women challenge recent national downward trends

Glasgow, the largest city in Scotland, has high levels of deprivation and a poor-health profile compared with other parts of Europe, which cannot be fully explained by the high levels of deprivation. The ‘excess’ premature mortality in Glasgow is now largely attributable to deaths from alcohol, drugs, suicide and violence. 
                               

Alcohol-related mortality in Glasgow from 1980 to 2011 was examined relative to the equally deprived UK cities of Manchester and Liverpool with the aim of identifying differences across the cities, with respect to gender, age and birth cohort, that could help explain the ‘excess’ mortality in Glasgow. 

                               

In the 1980s, alcohol-related mortality in Glasgow was three times higher than in Manchester and Liverpool. Alcohol-related mortality increased in all three cities over the subsequent three decades, but a sharp rise in deaths in the early 1990s was unique to Glasgow. The increase in numbers of deaths in Glasgow was greater than in Manchester and Liverpool, but there was little difference in the pattern of alcohol-related deaths, by sex or birth cohort that could explain the excess mortality in Glasgow. The recent modest decrease in alcohol-related mortality was largely experienced by all birth cohorts, with the notable exception of the younger cohort (born between 1970 and 1979): women in this cohort across all three cities experienced disproportionate increases in alcohol-related mortality. 

                               

It is imperative that this early warning sign in young women in the UK is acted on if deaths from alcohol are to reduce in the long term.

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NSW drops bans on alcohol discounts and youth celebrity promotions

Changes to state government regulations on the sale of alcohol in NSW have been heavily watered down to ditch proposed bans on huge discounts and promotions by celebrities who appeal to under-18s.
The new guidelines have lost many of the strict recommendations made in a draft from August last year, leading to accusations by the Labor opposition and Greens that the rules had been written by the alcohol industry and lobby.

The August draft ruled out “endorsements from celebrities or other role models that primarily appeal to minors as part of the liquor promotion”, reported Fairfax, but in the final guidelines the ban has become advice under “additional information” for venues to “take care”.  > > > >  Read More

Alcohol Strategy consultation report: PHE response

Public Health England responds to the Government's decision on minimum unit pricing.

Public Health England shares the disappointment of the public health community that the introduction of a minimum unit price (MUP) for alcohol is not being taken forward at this point, although it recognises that this remains under active consideration.

PHE exists to present the scientific evidence on the facts affecting the public’s health and to show where national and local action can best help improve it.  > > > >   Read More

Oral statement to Parliament - Government’s response to the alcohol strategy consultation

Minister of State for Crime Prevention Jeremy Browne gives a statement on the alcohol strategy consultation.

With permission, Mr Speaker, I shall make a statement on the government’s response to the alcohol strategy consultation. Today we are publishing an analysis of responses to the consultation, along with a “next steps” document. Copies of both are available in the House Library.

Drunken behaviour and alcohol-fuelled disorder can make towns and cities effective no-go areas for law-abiding people, particularly on Friday and Saturday nights. In nearly 50% of the incidents of violence that took place in 2011-12, the victim believed that the perpetrator was under the influence of alcohol. Excessive alcohol consumption costs the taxpayer huge amounts of money: alcohol-related crime and health harms are estimated to cost society about £21 billion every year. The government therefore have a role in seeking to curb excessive drinking. We have already increased duty on alcopops, and have introduced a wide-ranging set of reforms to tackle binge drinking.  > > > >  Read More

Global Actions: Commitments to Reduce Harmful Drinking. July 17, 2013

 

 

 

Global Actions in Focus

ICAP & CCDC Sign MOU

On July 5, 2013, ICAP and the Chinese Center for Disease Prevention and Control (CCDC) Office of Epidemiology signed a memorandum of understanding (MOU). The MOU solidifies ICAP’s partnership with the Office of Epidemiology to develop a capacity building toolkit for drink driving prevention in Phase II of the Global Actions Drink Driving Initiative. The toolkits will include teaching materials, lesson plans, teaching methods, auxiliary materials, teacher requirements, survey tools, and evaluation tools.

ICAP Senior Vice President Brett Bivans and Deputy Director Prof. Yao Hongyan sign the MOU on July 5, 2013, in Xi’an.

According to the MOU, the Office of Epidemiology will develop the Capacity Building Toolkit for Drink Driving Prevention, facilitating the capacity building workshops in Shenyang, and monitoring workshops in Jiangsu Province. Moreover, the organization will help ICAP engage local government agencies and be a vital resource for information and feedback.

Key Recent Milestones

· Russia: ICAP welcomes Margarita (Rita) Plotnikova as the new coordinator for the drink driving initiative in Moscow. Rita is an experienced communications and road safety manager who has worked for the International Federation of Red Cross and Red Crescent Societies (IFRC) and the Global Road Safety Partnership (GRSP). She will be working closely with the local sponsor companies to develop and implement the program.

What's Happening Next

· Mexico: Representatives will present drink driving awareness training to volunteer groups from the Puebla Legislative Power on July 26, 2013.

Government Alcohol Strategy response – Alcohol Research UK comment

 

Today the Government announced that it was abandoning plans to introduce a minimum unit price for alcohol.  It also dropped proposals to introduce a multibuy ban on sales in off-licenses and supermarkets.  In his introduction to the 2012 Alcohol Strategy David Cameron wrote that ‘we are going to introduce a new minimum unit price’, with a consultation on the right level at which it should be set.  This u-turn does not appear to be based on any new evidence, but rather a change of heart following sustained pressure from sections of the alcohol industry.

In his statement to Parliament, Jeremy Browne MP said 56% of respondents to the Alcohol Strategy consultation didn’t agree with a 45p minimum unit price, but was unable to say how many of those felt it should be actually be higher.

The Government now looks set to revert to its previous policy of banning the sale of alcohol at below cost + VAT.  However, previous analyses have found that this will have a negligible impact on drinks promotions and cheap alcohol sales.  > > > >  Read More

Funding Opportunity Announcements for Collaborative Research on Addiction at NIH (CRAN)

NIDA, NIAAA, and NCI announce the release of 2 new FOAs to promote the goals of Collaborative Research on Addiction at NIH (CRAN; formerly known as functional integration). Its mission is to provide a strong collaborative framework for enabling NIDA, NIAAA, and NCI to pool resources and expertise, creating synergies in addiction science, addressing new research opportunities, and meeting the public’s health needs.   > > > >  Read More

Genome-wide DNA methylation patterns in discordant sib pairs with alcohol dependence

Alcohol dependence is a complex disease caused by a confluence of environmental and genetic factors. Epigenetic mechanisms have been shown to play an important role in the pathogenesis of alcohol dependence.

 

To determine if alterations in gene-specific methylation were associated with alcohol dependence, a genome-wide DNA methylation analysis was performed on peripheral blood mononuclear cells from alcohol-dependent patients and siblings without alcohol dependence as controls. The Illumina Infinium Human Methylation450 BeadChip was used and gene-specific methylation of DNA isolated from peripheral blood mononuclear cells was assessed. Genes ALDH1L2, GAD1, DBH and GABRP were selected to validate beadchip results by pyrosequencing.

 

Compared to normal controls, 865 hypomethylated and 716 hypermethylated CG sites in peripheral blood mononuclear cell DNA in alcohol-dependent patients were identified. The most hypomethylated CG site is located in the promoter of SSTR4 (somatostatin receptor 4) and the most hypermethylated CG site is GABRP (gamma-aminobutyric acid A receptor). The results from beadchip analysis were consistent with that of pyrosequencing.
 

DNA methylation might be associated with alcohol dependence. Genes SSTR4, ALDH1L2, GAD1, DBH and GABRP may participate in the biological process of alcohol dependence.


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News Release - Ban on below-cost selling for alcohol would have smaller impact than a 45p minimum price

- Below-cost selling will have very little impact on alcohol consumption

- New policy will educe overall consumption by 0.04 per cent

- 1.3 per cent of all alcohol units sold will be affected by the ban

The Government will today (Wednesday 17 July 2013) announce plans to ban retailers from selling alcohol cheaper than the cost of the tax payable on the product. This ban on below-cost selling will have a very small impact on alcohol consumption and related harms according to the Sheffield Alcohol Research Group.

Experts, based at the University of Sheffield's School of Health and Related Research (ScHARR), whose research has been influential in providing evidence to inform policy decisions in the UK and beyond, analysed evidence on alcohol purchases in England under these new plans.

They estimated a small proportion (1.3 per cent) of all units of alcohol sold would fall below this proposed threshold. This varies by the type of drink, and in supermarkets and off-licenses it would affect 2.4 per cent of beer, just 0.1 per cent of cider, 0.4 per cent of wine and 1.2 per cent of spirits.   >  >  >  >   Read More

Role of cannabinoid CB2 receptor in the reinforcing actions of etha

This study examines the role of the cannabinoid CB₂ receptor (CB₂r) on the vulnerability to ethanol consumption.

The time-related and dose-response effects of ethanol on rectal temperature, handling-induced convulsions (HIC) and blood ethanol concentrations were evaluated inCB₂KO and wild-type (WT) mice. The reinforcing properties of ethanol were evaluated in conditioned place preference (CPP), preference and voluntary ethanol consumption and oral ethanol self-administration. Water-maintained behavior schedule was performed to evaluate the degree of motivation induced by a natural stimulus. Preference for non-alcohol tastants assay was performed to evaluate the differences in taste sensitivity. Tyrosine hydroxylase (TH) and μ-opioid receptor gene expressions were also measured in the ventral tegmental area and nucleus accumbens (NAcc), respectively. 

CB₂KO mice presented increased HIC score, ethanol-CPP, voluntary ethanol consumption and preference, acquisition of ethanol self-administration, and increased motivation to drink ethanol compared with WT mice.

No differences were found between genotypes in the water-maintained behavior schedule or preference for non-alcohol tastants. Naïve CB₂KO mice presented increased μ-opioid receptor gene expression in NAcc. Acute ethanol administration (1–2 g/kg) increased TH and μ-opioid receptor gene expressions in CB₂KO mice, whereas the lower dose of ethanol decreased TH gene expression in WT mice.

These results suggest that deletion of the CB₂r gene increased preference for and vulnerability to ethanol consumption, at least in part, by increased ethanol-induced sensitivity of the TH and μ-opioid receptor gene expressions in mesolimbic neurons.

Future studies will determine the role of CB₂r as a target for the treatment of problems related with alcohol consumption.




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Request Reprint E-Mail:    jmanzanares@umh.es

Letter to the Editor - On French and American paradoxes

We would like to thank Dr Lanzmann-Petithory for her comments [1] on our age–period–cohort analyses about heavier drinking [2]. As she devoted most of the space to alcohol and health in general and the French paradox in particular, we would like to start our rejoinder with a remark on that topic. The role of wine in the French paradox is still controversial. It is now known that a large part of this seeming paradox can be explained by the coding practices of French doctors, who have been shown to overuse unspecific codes for cardiovascular disease, so-called ‘garbage codes’, artificially lowering the prevalence of ischaemic heart disease [3, 4]. As for the general impact of alcohol on health, most analyses come to the conclusion that it is mostly detrimental [e.g. [5]; the latest results of the Global Burden of Diseases study (GBD): http://www.healthmetricsandevaluation.org/gbd/research/project/global-burden-diseases-injuries-and-risk-factors-study-2010].
> > >    Read More

Preventing alcohol harm: Early results from a cluster randomised, controlled trial in Victoria, Australia of comprehensive harm minimisation school drug educatio

 

 

 

In Australia, the burden of alcohol-attributable harm falls most heavily on young people. Prevention is important, and schools have long been seen as appropriate settings for pre-emptive interventions with this high risk group. This paper evaluates the effectiveness, in relation to alcohol harm prevention, of the Drug Education in Victorian Schools (DEVS) programme, nine months after implementation. This intervention dealt with both licit and illicit drugs, employed a harm minimisation approach that incorporated interactive, skill based, teaching methods and capitalised on parental influence through home activities.

 

A cluster randomised, controlled trial of the first ten lessons of the DEVS drug education programme was conducted with year eight students, aged 13–14 years. Twenty-one secondary schools in Victoria, Australia were randomly allocated to receive the DEVS programme (14 schools, n = 1163) or the drug education usually provided by their schools (7 schools, n = 589). Self-reported changes were measured in relation to: knowledge and attitudes, communication with parents, drug education lessons remembered, proportion of drinkers, alcohol consumption (quantity multiplied by frequency), proportion of student drinkers engaging in risky consumption, and the number of harms experienced as a result of alcohol consumption.

 

In comparison to the controls, there was a significantly greater increase in the intervention students’ knowledge about drugs, including alcohol (p ≤ 0.001); there was a significant change in their level of communication with parents about alcohol (p = 0.037); they recalled receiving significantly more alcohol education (p < 0.001); their alcohol consumption increased significantly less (p = 0.011); and they experienced a lesser increase in harms associated with their drinking (p ≤ 0.001). There were no significant differences between the two study groups in relation to changes in attitudes towards alcohol or in the proportion of drinkers or risky drinkers. There was, however, a notable trend of less consumption by risky drinkers in the intervention group.

 

A comprehensive, harm minimisation focused school drug education programme is effective in increasing general drug knowledge, and reducing alcohol consumption and harm.

 

 

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Request Reprint E-Mail:     r.midford@ecu.edu.au

Alcohol News - 28/2013

 Radio Sweden (Sweden) - State alcohol shop sues food

chain over online wine offer

A government-sponsored report has suggested tighter controls of alcohol marketing, after it increased markedly in the last few years. Meanwhile, monopoly alcohol retailer Systembolaget has sued the food retail chain City Gross for announcing recently that online customers would be offered wine for purchase.

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Radio Sweden (Sweden) - Alcohol sales fall

Alcohol sales from Sweden's state-owned alcohol sales (off-licence) monopoly Systembolaget fell by 2.2 percent between March and June 2013 compared to the same period last year, according to new figures.

Read more

News ERR (Estonia) - Alcohol, Tobacco Still Eroding Healthy Life Expectancy, Experts Say

Healthy life expectancy has dropped in the last three years to just 55.5 - seven years off the EU average. Experts point to a combination of increased tobacco and alcohol use and financial insecurity from the last recession.

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NordAN - Alcohol advertising in Nordic and Baltic countries

Nordic Alcohol and Drug Policy Network (NordAN) is focusing on alcohol advertising and its role to drinking and especially on young peoples relationship to alcohol in Nordic-Baltic region.

Read more

Stuff.co.nz - Alcohol strongly linked to cancer – study

Alcohol has been identified as one of the leading contributors to breast cancer deaths in a University of Otago study.

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WalesOnline (Wales) - Binge drinkers to be filmed and shown their behaviour as alcohol treatment centre hailed a success

A teacher passed out in a taxi, a student saved from hypothermia and a French foreign exchange student glassed were among those helped at a world-first alcohol treatment centre.

Read more

New York Daily News (USA) - Alcohol labeling: Coming to a liquor store near you

People tend to overlook 'liquid calories,' particularly those that come from alcoholic beverages – because if you don't chew, it seems like it doesn't count. Sadly, that's not the case.

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Northern Star - Legalise drug to curb drinking says alcohol research expert

THE head of Australia's leading alcohol research body has said that marijuana should be legalised in an effort to curb binge drinking.

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Metro.us - Preschool habits can predict future alcohol use, according to a new study

A new study shows that how children act before they reach age five might predict their alcohol use a decade later.

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Telegraph.co.uk (UK) - 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.

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UPI.com (USA) - Alcohol making more appearances in movies for U.S. Teens

Branded alcohol is making more and more appearances in movies rated for U.S. teen audiences, a researcher says.

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Scotsman (UK) - Alcohol pricing: SNP to press ahead on price law

THE Health Secretary Alex Neil yesterday underlined his determination to press ahead with alcohol minimum pricing, saying he is fully committed to the “life-saving” policy.

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Toronto NewsFIX - Women Drinking Alcohol at Increased Risk of Numerous Cancers

Women who drink alcohol are unknowingly putting themselves at increased risk of cancer. This is the finding of a study performed by researchers from Britain’s University of Oxford, who studied more than 1.3 million women.

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The Local.es (Spain) - Spain raises taxes on alcohol and tobacco

The Spanish government, which is struggling to cut one of the eurozone's largest public deficits during a double-dip recession, on Friday raised taxes on tobacco and alcohol, except wine and beer.

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News-Medical.net - Smoking and heavier alcohol consumption speed up cognitive decline

The combination of smoking and heavy drinking speeds up cognitive decline, according to new research published in the British Journal of Psychiatry.

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Irish Mirror (Ireland) - We're paying the tab for our costly booze culture

There is no doubt we have a very unhealthy relationship with alcohol. Is this another result of both the Celtic Tiger and its demise?

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The Sidney Morning Herald (Australia) - Government bows to liquor industry on discounts

Supermarket giants have strongarmed the state government into backing out of its planned ban on shopper docket alcohol discounts.

Read more

 

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