Part of the brain for 'hangover guilt' identified

Behind the Headlines

Monday June 30 2014

The research may offer insights into why people continue to drink, even though it is harmful.

The rats were given free access to alcohol

"Scientists pinpoint the part of the brain that tells us 'never again'," the Mail Online reports. New research in rats suggests part of the brain called the lateral habenula (LHb) helps us learn lessons from bad experiences after consuming too much alcohol.

The LHb is believed to play some role in preventing us repeating something that previously resulted in a negative outcome, such as getting extremely drunk and waking up with a dreadful hangover. But some people may lack activity in this part of the brain.

This study found causing surgical damage to the LHb stopped it having inhibitory effects on alcohol consumption. When given free access to alcohol, rats that did not have damage to this part of the brain had a high alcohol intake initially, but this then tailed off. Rats with LHb damage showed a continuously increasing rate of ethanol consumption.

A similar mechanism may play a role in people with alcohol misuse problems. As a result of decreased LHb activity, they may fail to "learn" from alcohol-associated adverse events and continue to misuse the drug. This may explain why many people who experience the negative effects of alcohol continue to drink.

But intriguing as this hypothesis is, it remains unproven. The research also has no direct implications for humans at this stage, such as new ways to prevent and treat alcohol dependence.

 

Where did the story come from?

The study was carried out by researchers from the University of Utah School of Medicine in the US, and was funded by the US National Institutes of Health, the March of Dimes Foundation and the University of Utah.

It was published in the peer-reviewed scientific journal PLOS One. PLOS One is an open access journal, so the article is free to read online.

The Mail Online's reporting of the study is accurate.

 

What kind of research was this?

This was animal research that aimed to investigate the role of a particular region of the brain – the lateral habenula (LHb) – in conditioning our response to alcohol.

The LHb has been implicated as a brain region key in learning from adverse outcomes. It is believed to play a role in stopping us doing things if we had a negative experience when we did this previously.

As the researchers say, the positive effects of drugs are known to motivate further drug-seeking behaviours. But it is also known that the adverse effects of drugs can limit further intake.

Previous studies pointed towards the LHb being involved in reducing motivation to consume nicotine and cocaine.

Ethanol (alcohol) is well known to have downsides, including impairment of motion and hangovers.

Studies have shown that rats with sensitivity to these adverse effects decrease their voluntary intake of alcohol.

To further examine the role of the LHb in learning driven by adverse outcomes, the researchers studied voluntary ethanol consumption in rats with and without lesions (damage) in the LHb. 

 

What did the research involve?

The research involved 136 male rats. The rats were anaesthetised and half were given surgical damage to the LHb by passing an electrical current through it. The remainder of the rats received a similar surgery, but no electrical current was passed (a "sham" procedure).

The rats were given one week to recover before being included in various experiments. The researchers conducted various experiments looking at the role of the LHb in alcohol consumption.

In one experiment, sham and lesion rats (17 in each group) were given intermittent 24-hour access to two bottles over eight weeks. One bottle contained water and one contained a solution of water with ethanol (alcohol) at a concentration of 20%. On some days, they were given only water and no ethanol.

The researchers weighed the water and ethanol bottles to measure intake and preference. After eight weeks, they looked at various effects in subsets of rats, including looking at the effect of subjecting the rats to a long period of alcohol abstinence before restoring their alcohol intake.

Another group of sham and lesion rats (10 in each group) were given intermittent 24-hour ethanol access for eight weeks. The researchers then examined the effects of allowing the rats access to self-administer ethanol by pressing a lever. After a period of free self-delivery, the researchers tested what happened when pressing the lever no longer gave the rats alcohol.   

As a final test in a large group of 37 sham and 42 lesion rats, the researchers tested the theory of conditioned taste aversion, where an effect of one fluid conditions them to dislike fluids with a similar taste, even if they don't have the same effect.

These rats were housed with free access to food and water and a sugar solution. They were then given ethanol, and the subsequent effect on their consumption of sugar solution was measured.

 

What were the basic results?

The researchers found that intermittent 24-hour ethanol access resulted in a steady increase in ethanol consumption in both sham and LHb lesion rats.

However, after one week of ethanol, consumption in the lesion rats increased more than the sham rats and reached higher intake levels, reaching 6g per kg per 24 hours, compared with 4g per kg per 24 hours in the sham rats.

The rats with the LHb lesions continued to show higher intake than the sham rats when they were not given alcohol for a period before access was then reinstated.

After the eight weeks of intermittent ethanol access, the researchers found the LHb lesion rats pressed the lever to get alcohol significantly more than the sham rats.

When the lever presses no longer rewarded them with ethanol, the lesion rats still pressed the lever more than the sham rats on the first day, but not after that.

In the final test of conditioned taste aversion, after giving rats ethanol, those with no LHb damage also showed an aversion to drinking the sugary solution, while those with LHb damage did not show aversion.

 

How did the researchers interpret the results?

The researchers concluded that their results show that the lateral habenula (LHb) plays an important role in controlling ethanol-directed behaviours.

 

Conclusion

This was animal research that aimed to investigate the role of the lateral habenula (LHb) in conditioning responses to alcohol.

The LHb is a brain region key in learning driven by adverse outcomes. It is believed to play a role in stopping us repeating actions that have previously resulted in negative outcomes.

In this study in rats, surgical damage to the LHb stopped the rats learning to moderate their alcohol consumption.

When given free and open access to ethanol, rats with LHb damage showed continuously increasing rates of ethanol consumption and reached higher blood alcohol levels.

Comparatively, rats without damage to this brain region had a high intake initially, but their liking then tailed off.

The researchers also found damage to the LHb reduced conditioned taste aversion – after being given ethanol, rats without damage to this region had an aversion to drinking a sugar solution, but the rats with LHb damage did not.

Overall, this rat study supports the belief that the LHb may be involved in learning driven by adverse outcomes. But it isn't clear what negative effects the rats could have been having – for example, whether this was linked to them having anything like a hangover after drinking alcohol.

The direct implications for humans are currently very limited. It is plausible that some people have an underperforming LHb. This could lead to self-destructive patterns of behaviour, despite a previous history of adverse events such as hangovers.

Even if this highly speculative hypothesis turns out to be true, it is currently unclear what treatments this could lead to.

Current treatments for alcohol misuse include medications that can help relieve cravings, as well as counselling – both one-to-one and in groups.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Analysis by Bazian

Edited by NHS Choices

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Media last reviewed: 17/06/2015

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