alcohol-consumption

Drunk Dial 2/2

Part 1

“Often people display a curious respect for a man drunk… There is something awe-inspiring in one who has lost all inhibitions.”

- F. Scott Fitzgerald


It’s not nearly as bad as he’d thought.

The party was full of over-excited, but good natured teens who had gotten a bit over-zealous in their alcohol consumption. He had even managed to get Kate not to call it in. His daughter is going to have her first hangover and one hell of a headache come morning, but she’ll be okay and that settles him.

Now, Castle is rummaging through his medicine cabinet for aspirin while Kate helps Alexis up the stairs to her room.

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Sam + alcohol

A gene mutation for excessive alcohol drinking found

Researchers have discovered a gene that regulates alcohol consumption and when faulty can cause excessive drinking. They have also identified the mechanism underlying this phenomenon.

The study showed that normal mice show no interest in alcohol and drink little or no alcohol when offered a free choice between a bottle of water and a bottle of diluted alcohol.

However, mice with a genetic mutation to the gene Gabrb1 overwhelmingly preferred drinking alcohol over water, choosing to consume almost 85% of their daily fluid as drinks containing alcohol - about the strength of wine.

The consortium of researchers from five UK universities – Newcastle University, Imperial College London,  Sussex University, University College London and University of Dundee – and the MRC Mammalian Genetics Unit at Harwell, funded by the Medical Research Council (MRC), Wellcome Trust and ERAB, publish their findings today in Nature Communications.

Dr Quentin Anstee, Consultant Hepatologist at Newcastle University, joint lead author said: “It’s amazing to think that a small change in the code for just one gene can have such profound effects on complex behaviours like alcohol consumption.

“We are continuing our work to establish whether the gene has a similar influence in humans, though we know that in people alcoholism is much more complicated as environmental factors come into play. But there is the real potential for this to guide development of better treatments for alcoholism in the future.”

Identifying the gene for alcohol preference

Working at the MRC Mammalian Genetics Unit, a team led by Professor Howard Thomas from Imperial College London introduced subtle mutations into the genetic code at random throughout the genome and tested mice for alcohol preference. This led the researchers to identify the gene Gabrb1 which changes alcohol preference so strongly that mice carrying either of two single base-pair point mutations in this gene preferred drinking alcohol (10% ethanol v/v - about the strength of wine), over water.

The group showed that mice carrying this mutation were willing to work to obtain the alcohol-containing drink by pushing a lever and, unlike normal mice, continued to do so even over long periods. They would voluntarily consume sufficient alcohol in an hour to become intoxicated and even have difficulty in coordinating their movements.

The cause of the excessive drinking was tracked down to single base-pair point mutations in the gene Gabrb1, which codes for the beta 1 subunit, an important component of the GABAA receptor in the brain. This receptor responds to the brain’s most important inhibitory chemical messenger (GABA) to regulate brain activity. The researchers found that the gene mutation caused the receptor to activate spontaneously even when the usual GABA trigger was not present.

These changes were particularly strong in the region of the brain that controls pleasurable emotions and reward, the nucleus accumbens, as Dr Anstee explains: “The mutation of the beta1 containing receptor is altering its structure and creating spontaneous electrical activity in the brain in this pleasure zone, the nucleus accumbens. As the electrical signal from these receptors increases, so does the desire to drink to such an extent that mice will actually work to get the alcohol, for much longer than we would have expected.”

Professor Howard Thomas said: “We know from previous human studies that the GABA system is involved in controlling alcohol intake. Our studies in mice show that a particular subunit of GABAA receptor has a significant effect and most importantly the existence of these mice has allowed our collaborative group to investigate the mechanism involved. This is important when we come to try to modify this process first in mice and then in man.”

Leading to a treatment for alcohol addiction

Initially funded by the MRC, the 10-year project aimed to find genes affecting alcohol consumption. Professor Hugh Perry, Chair of the MRC’s Neurosciences and Mental Health Board, said: “Alcohol addiction places a huge burden on the individual, their family and wider society. There’s still a great deal we don’t understand about how and why consumption progresses into addiction, but the results of this long-running project suggest that, in some individuals, there may be a genetic component. If further research confirms that a similar mechanism is present in humans, it could help us to identify those most at risk of developing an addiction and ensure they receive the most effective treatment.”

Most colleges require students to go through some sort of alcohol education program. When I was a freshman in college, I was required to play a video game that involved helping Franklin the frog navigate through various college parties without succumbing to alcohol poisoning. (Easy, Frank — remember to hydrate).

Other universities require students to watch educational videos or take online quizzes about appropriate alcohol use.These one-time interventions do work, but their effect tends to wear off as the school year progresses, according to a recent study.

Programs Help Students Cut Back On Booze, But Not For Long

Photo Credit: iStockphoto

Researchers Identify Key Factor in Transition from Moderate to Problem Drinking

A team of UC San Francisco researchers has found that a tiny segment of genetic material known as a microRNA plays a central role in the transition from moderate drinking to binge drinking and other alcohol use disorders.

Previous research in the UCSF laboratory of Dorit Ron, PhD, Endowed Chair of Cell Biology of Addiction in Neurology, has demonstrated that the level of a protein known as brain-derived neurotrophic factor, or BDNF, is increased in the brain when alcohol consumed in moderation. In turn, experiments in Ron’s lab have shown, BDNF prevents the development of alcohol use disorders.

In the new study, Ron and first author Emmanuel Darcq, PhD, a former postdoctoral fellow now at McGill University in Canada, found that when mice consumed excessive amounts of alcohol for a prolonged period, there was a marked decrease in the amount of BDNF in the medial prefrontal cortex (mPFC), a brain region important for decision making. As reported in the October 21, 2014 online edition of Molecular Psychiatry, this decline was associated with a corresponding increase in the level of a microRNA called miR-30a-5p.

MicroRNAs lower the levels of proteins such as BDNF by binding to messenger RNA, the molecular middleman that carries instructions from genes to the protein-making machinery of the cell, and tagging it for destruction.

Ron and colleagues then showed that if they increased the levels of miR-30a-5p in the mPFC, BDNF was reduced, and the mice consumed large amounts of alcohol. When mice were treated with an inhibitor of miR-30a-5p, however, the level of BDNF in the mPFC was restored to normal and alcohol consumption was restored to normal, moderate levels.

“Our results suggest BDNF protects against the transition from moderate to uncontrolled drinking and alcohol use disorders,” said Ron, senior author of the study and a professor in UCSF’s Department of Neurology. “When there is a breakdown in this protective pathway, however, uncontrolled excessive drinking develops, and microRNAs are a possible mechanism in this breakdown. This mechanism may be one possible explanation as to why 10 percent of the population develop alcohol use disorders and this study may be helpful for the development of future medications to treat this devastating disease.”

One reason many potential therapies for alcohol abuse have been unsuccessful is because they inhibit the brain’s reward pathways, causing an overall decline in the experience of pleasure. But in the new study, these pathways continued to function in mice in which the actions of miR-30a-5p had been tamped down—the mice retained the preference for a sweetened solution over plain water that is seen in normal mice.

This result has significant implications for future treatments, Ron said. “In searching for potential therapies for alcohol abuse, it is important that we look for future medications that target drinking without affecting the reward system in general. One problem with current alcohol abuse medications is that patients tend to stop taking them because they interfere with the sense of pleasure.”

Researchers find that alcohol consumption damages brain’s support cells

Alcohol consumption affects the brain in multiple ways, ranging from acute changes in behavior to permanent molecular and functional alterations. The general consensus is that in the brain, alcohol targets mainly neurons. However, recent research suggests that other cells of the brain known as astrocytic glial cells or astrocytes are necessary for the rewarding effects of alcohol and the development of alcohol tolerance. The study, first-authored by Dr. Leonardo Pignataro, was published in the February 6th issue of the scientific journal Brain and Behavior.

“This is a fascinating result that we could have never anticipated. We know that astrocytes are the most abundant cell type in the central nervous system and that they are crucial for neuronal growth and survival, but so far, these cells had been thought to be involved only in brain’s support functions. Our results, however, show that astrocytes have an active role in alcohol tolerance and dependence,” explains Dr. Pignataro.

The team of researchers from Columbia and Yale Universities analyzed how alcohol exposure changes gene expression in astrocyte cells and identified gene sets associated with stress, immune response, cell death, and lipid metabolism, which may have profound implications for normal neuronal activity in the brain. “Our findings may explain many of the long-term inflammatory and degenerative effects observed in the brain of alcoholics,” says Dr. Pignataro. “The change in gene expression observed in alcohol-exposed astrocytes supports the idea that some of the alcohol consumed reaches the brain and that ethanol (the active component of alcoholic beverages) is locally metabolized, increasing the production free radicals that react with cell components to affect the normal function of cells. This activates a cellular stress response in the cells in an attempt to defend from this chemical damage. On the other hand, the body recognizes these oxidized molecules as "foreign objects” generating an immune response against them that leads to the death of damage cells. This mechanism can explain the inflammatory degenerative process observed in the brain of chronic alcoholics, allowing for the development of different and novel therapeutically approaches to treat this disease" added Dr. Pignataro.

The consequences of alcohol on astrocytes revealed in this study go far beyond what happens to this particular cell type. Astrocytes play a crucial role in the CNS, supporting normal neuronal activity by maintaining homeostasis. Therefore, alcohol changes in gene expression in astrocytes may have profound implications for neuronal activity in the brain.

These findings will help scientists better understand alcohol-associated disorders, such as the brain neurodegenerative damage associated with chronic alcoholism and alcohol tolerance and dependence. “We hope that this newly discovered role of astrocytes will give scientists new targets other than neurons to develop novel therapies to treat alcoholism,” Leonardo Pignataro concluded.

Pre-sleep drinking disrupts sleep

For individuals who drink before sleeping, alcohol initially acts as a sedative - marked by the delta frequency electroencephalogram (EEG) activity of Slow Wave Sleep (SWS) - but is later associated with sleep disruption. Significant reductions in EEG delta frequency activity and power also occur with normal development between the ages of 12 and 16; likewise this is a time when alcohol is commonly consumed for the first time, with dramatic increases in drinking occurring among collage-age individuals. A study of the effects of alcohol on sleep EEG power spectra in college students has found that pre-sleep drinking not only causes an initial increase in SWS-related delta power but also causes an increase in frontal alpha power, which is thought to reflect disturbed sleep.

Results will be published in the February 2015 online-only issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

“People likely tend to focus on the commonly reported sedative properties of alcohol, which is reflected in shorter times to fall asleep, particularly in adults, rather than the sleep disruption that occurs later in the night,” said Christian L. Nicholas, National Health & Medical Research Council Peter Doherty Research Fellow in the Sleep Research Laboratory at The University of Melbourne as well as corresponding author for the study.

“The reduction in delta frequency EEG activity we see across the ages is thought to represent normal brain maturational processes as the adolescent brain continues to develop to full maturity,” said Nicholas. “Although the exact function of non-Rapid Eye Movement (NREM) sleep, and in particular SWS, is a topic of debate, it is thought to reflect sleep need and quality; thus any disruption to this may affect the underlying restorative properties of sleep and be detrimental to daytime functioning.”

Nicholas and his colleagues recruited 24 participants (12 female, 12 male), healthy 18- to 21-year-old social drinkers who had consumed less than seven standard drinks per week during the previous 30 days. Each participant underwent two conditions: pre-sleep alcohol as well as a placebo, followed by standard polysomnography with comprehensive EEG recordings.

Results showed that alcohol increased SWS delta power during NREM. However, there was a simultaneous increase in frontal alpha power.

“For individuals researching sleep in the field of alcohol studies,” said Nicholas, “our findings indicate that care needs to be taken when interpreting increases in ‘visually scored’ SWS associated with alcohol consumption. Increases in SWS, which traditionally would be interpreted as a good thing, can be associated with more subtle changes indicating disrupted sleep, such as the increases we observed in alpha activity, which are revealed when more detailed micro-structural components of the sleep electroencephalogram are assessed.”

Nicholas explained that the increase in frontal alpha power that occurs as a result of pre-sleep drinking likely reflects a disruption of the normal properties of NREM slow wave sleep.

“Similar increases in alpha-delta activity, which are associated with poor or unrefreshing sleep and daytime function, have been observed in individuals with chronic pain conditions,” he said. “Thus, if sleep is being disrupted regularly by pre-sleep alcohol consumption, particularly over long periods of time, this could have significant detrimental effects on daytime wellbeing and neurocognitive function such as learning and memory processes.”

Alcohol is not a sleep aid, said Nicholas. “The take-home message here is that alcohol is not actually a particularly good sleep aid even though it may seem like it helps you get to sleep quicker. In fact, the quality of the sleep you get is significantly altered and disrupted.”

The Ground Far Below: A Korrasami Wedding Day fic

[Written for Korrasami Wedding Day. I cheated a little, because I wanted to a prompt from this list – in this case, “We’ve been dating forever, and you just caught the bouquet at our friend’s wedding." So it’s more Korrasami engagement than wedding, but hopefully still cute!

Korra and Asami get ready for Opal and Bolin’s wedding. T, 3.2k words. Entirely fluff.]

The Ground Far Below

The alarm clock blared to deafening, hateful life. Korra pulled another pillow on top of her head with a dramatic groan. It drowned out the ringing and the traces of light invading through the drawn curtains, but somehow couldn’t block the sound of Asami pointedly clearing her throat.

“Korra.”

She made a strangled, pleading noise into the pillows.

“I’m going to interpret that as ‘Yes, Asami, you were right about Opal’s bachelorette party, and you are a gem among women for making me hangover breakfast.'”

The spike of horror that shot through Korra made her sit straight up, knocking her improvised pillow fort to the ground.

“Is the kitchen on fire? You know you can aways drag me out of bed if the kitchen’s on fire.”

Asami was smirking, leaning in the doorway of the bedroom with her arms crossed. “I don’t see why we have to keep bringing that up. Okay, so this gem-among-women brought you carry-out from the diner. And,” Asami unfolded her arms and strode over the the bed, “that got you more or less upright, so it’s been a pretty successful morning.”

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