A Brain Region for Resisting Alcohol’s Allure

As recovering spring breakers are regretting binge drinking escapades, it may be hard for them to appreciate that there is a positive side to the nausea, sleepiness, and stumbling. University of Utah neuroscientists report that when a region of the brain called the lateral habenula is chronically inactivated in rats, they repeatedly drink to excess and are less able to learn from the experience. The study, published online in PLOS ONE on April 2, has implications for understanding behaviors that drive alcohol addiction.

While complex societal pressures contribute to alcoholism, physiological factors are also to blame. Alcohol is a drug of abuse, earning its status because it tickles the reward system in the brain, triggering the release of feel-good neurotransmitters. The dreaded outcomes of overindulging serve the beneficial purpose of countering the pull of temptation, but little is understood about how those mechanisms are controlled.

U of U professor of neurobiology and anatomy Sharif Taha, Ph.D., and colleagues, tipped the balance that reigns in addictive behaviors by inactivating in rats a brain region called the lateral habenula. When the rats were given intermittent access to a solution of 20% alcohol over several weeks, they escalated their alcohol drinking more rapidly, and drank more heavily than control rats.

“In people, escalation of intake is what eventually separates a social drinker from someone who becomes an alcoholic,” said Taha. “These rats drink amounts that are quite substantial. Legally they would be drunk if they were driving.”

The lateral habenula is activated by bad experiences, suggesting that without this region the rats may drink more because they fail to learn from the negative outcomes of overindulging. The investigators tested the idea by giving the rats a desirable, sweet juice then injecting them with a dose of alcohol large enough to cause negative effects.

“It’s the same kind of learning that mediates your response in food poisoning. You taste something and then you get sick, and then of course you avoid that food in future meals,” explained Taha.

Yet rats with an inactivated lateral habenula sought out the juice more than control animals, even though it meant a repeat of the bad experience.

“The way I look at it is the rewarding effects of drinking alcohol compete with the aversive effects,” explained Andrew Haack, who is co-first author on the study with Chandni Sheth, both neuroscience graduate students. “When you take the aversive effects away, which is what we did when we inactivated the lateral habenula, the rewarding effects gain more purchase, and so it drives up drinking behavior.”

The group’s findings may help explain results from previous clinical investigations demonstrating that men who were less sensitive to the negative effects of alcohol drank more heavily, and were more likely to become problem drinkers later in life.

The researches think the lateral habenula likely works in one of two ways. The region may regulate how badly an individual feels after over-drinking. Alternatively, it may control how well an individual learns from their bad experience. Future work will resolve between the two.

“If we can understand the brain circuits that control sensitivity to alcohol’s aversive effects, then we can start to get a handle on who may become a problem drinker,” said Taha.

Scientists find brain region that helps you make up your mind

One of the smallest parts of the brain is getting a second look after new research suggests it plays a crucial role in decision making.

A University of British Columbia study published today in Nature Neuroscience says the lateral habenula, a region of the brain linked to depression and avoidance behaviours, has been largely misunderstood and may be integral in cost-benefit decisions.

“These findings clarify the brain processes involved in the important decisions that we make on a daily basis, from choosing between job offers to deciding which house or car to buy,” says Prof. Stan Floresco of UBC’s Dept. of Psychology and Brain Research Centre (BRC). “It also suggests that the scientific community has misunderstood the true functioning of this mysterious, but important, region of the brain.”

In the study, scientists trained lab rats to choose between a consistent small reward (one food pellet) or a potentially larger reward (four food pellets) that appeared sporadically. Like humans, the rats tended to choose larger rewards when costs—in this case, the amount of time they had to wait before receiving food–were low and preferred smaller rewards when such risks were higher.

Previous studies suggest that turning off the lateral habenula would cause rats to choose the larger, riskier reward more often, but that was not the case. Instead, the rats selected either option at random, no longer showing the ability to choose the best option for them.

The findings have important implications for depression treatment. “Deep brain stimulation – which is thought to inactivate the lateral habenula — has been reported to improve depressive symptoms in humans,” Floresco says. “But our findings suggest these improvements may not be because patients feel happier. They may simply no longer care as much about what is making them feel depressed.”

Background

Floresco, who conducted the study with PhD candidate Colin Stopper, says more investigation is needed to understand the complete brain functions involved in cost-benefit decision processes and related behaviour. A greater understanding of decision-making processes is also crucial, they say, because many psychiatric disorders, such as schizophrenia, stimulant abuse and depression, are associated with impairments in these processes.

The lateral habenula is considered one of the oldest regions of the brain, evolution-wise, the researchers say.

Getting a grip on sleep

All mammals sleep, as do birds and some insects. However, how this basic function is regulated by the brain remains unclear. According to a new study by researchers from the RIKEN Brain Science Institute, a brain region called the lateral habenula plays a central role in the regulation of REM sleep. In an article published today in the Journal of Neuroscience, the team shows that the lateral habenula maintains and regulates REM sleep in rats through regulation of the serotonin system. This study is the first to show a role of the lateral habenula in linking serotonin metabolism and sleep.

The lateral habenula is a region of the brain known to regulate the metabolism of the neurotransmitter serotonin in the brain and to play a key role in cognitive functions.

“Serotonin plays a central role in the pathophysiology of depression, however, it is not clear how abnormalities in regulation of serotonin metabolism in the brain lead to symptoms such as insomnia in depression,” explain Dr. Hidenori Aizawa and Dr. Hitoshi Okamoto who led the study.

Since animals with increased serotonergic activity at the synapse experienced less REM sleep, the researchers hypothesized that the lateral habenula, which regulates serotonergic activity in the brain, must modulate the duration of REM sleep.

They show that removing the lateral habenula in rats results in a reduction of theta rhythm, an oscillatory activity that appears during REM sleep, in the hippocampus, and shortens the rats’ REM sleep periods. However, this inhibitory effect of the lateral habenular lesion on REM sleep disappears when the serotonergic neurons in the midbrain are lesioned.

The team recorded neural activity simultaneously in the lateral habenula and hippocampus in a sleeping rat. They find that the lateral habenular neurons, which fire persistently during non-REM sleep, begin to fire rhythmically in accordance with the theta rhythm in the hippocampus when the animal is in REM sleep.

“Our results indicate that the lateral habenula is essential for maintaining theta rhythms in the hippocampus, which characterize REM sleep in the rat, and that this is done via serotonergic modulation,” concludes Dr Aizawa.

“This study reveals a novel role of the lateral habenula, linking serotonin and REM sleep, which suggests that an hyperactive habenula in patients with depression may cause altered REM sleep,” add the authors.