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Scripps Research shows how cravings for alcohol increase after drinking alcohol during abstinence. – Researcher


For some people with an alcohol disorder it may be a look at a familiar bar or a favorite bottle; for others it may be the feeling of leaving the office after a busy day or attending a crowded party. Most people who struggle with drug or alcohol addiction have certain signals that trigger their cravings.

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Now, researchers at Scripps Research have found that in alcohol-dependent rats, the environmental signals associated with alcohol use during withdrawal are much stronger than those learned in the early stages of alcohol use, leading to more insurmountable cravings. New findings published online in British Journal of Pharmacologymay eventually lead to new treatments to minimize cravings in people with addictions.

“We already knew that cravings caused by environmental stimuli tend to increase over time with severe alcohol use disorders,” says Friedbert Weiss, Ph.D., professor at Scripps Research, “but no one has teased, both behaviorally and neurobiologically. . why so far.

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Evaluation 14.5 million people in the United States have a disorder of alcohol use that covers a number of harmful behaviors when drinking alcohol. Like other addictions, alcohol dependence is characterized by cycles of withdrawal, abstinence, and relapse. Traction caused by environmental stimuli – as well as those present when passing a local bar – is a powerful stimulus for relapse. Similarly, rats that have learned to associate a certain odor with alcohol will look for alcohol when exposed to the odor.

In a new paper, Weiss and colleagues sought to understand whether the experience of repeated alcohol use during abstinence, rather than just the length of time or severity of addiction, helps to reinforce the associations studied that lead to cravings. They taught rats who were not addicted to alcohol to associate the smell of anise or orange with alcohol. A subset of these animals then went through abstinence cycles during which they were conditioned to associate a different odor with alcohol use.

“This allowed us for the first time to separate the training that takes place during the initial, independent state and the training that takes place during the failure,” Weiss says.

When all the animals were tested to see how much they would go for alcohol in the presence of air conditioning odor, the Weiss group found that the signals received during the refusal were much more responsive. In other words, the experience of studying how alcohol relieves negative withdrawal symptoms has led to even greater cravings than the initial experience of studying the effects of alcohol on well-being.

“It is generally believed that people drink because it makes them feel good. But in people who have developed an addiction, the “feeling of well-being” that the drug causes actually cancels out the feeling of being horrible, “says Weiss. “If this opposite feeling of horror is experienced repeatedly, then the environmental signals associated with that experience evoke a much stronger craving than the initial desire to‘ feel good ’.

Rats that learned to associate odor with alcohol during withdrawal were much more persistent in the presence of that odor; for a 30-minute period of time they pressed the lever, trying to get alcohol twice as often as animals that were conditioned only during early alcohol consumption had not yet become addicted. This persistence remained even when they received a small electric shock when pressing the lever or when the task of pressing the lever became increasingly difficult.

“If an alcoholic comes home from work and there is nothing in the fridge, how much will he go for alcohol? Will they run around next to the liquor store? What if it’s snowing outside and the store is a five mile walk? We see that in rats they will work much harder to overcome obstacles, and are willing to suffer adverse consequences if they were caused by signals during the retreat, ”says Weiss.

What’s more, the team found that the new conditioning actually weakened old signals that had been studied before the animal became addicted to alcohol. If the animal originally associated alcohol with the smell of anise, but later became addicted and caused to associate alcohol with the smell of orange during alcohol withdrawal, the smell of anise was no longer such a strong signal to induce alcohol-seeking behavior compared to the second smell , which has been linked to alcohol use during abstinence.

The researchers then studied the amygdala, the part of the brain associated with drug and alcohol addiction in humans and rats, to see how it changed during each conditioning experiment. They found that different sites were activated depending on whether rats assimilated the odor during the initial exposure to alcohol, if not addicted, or during rejection after they became addicted.

“Discovering the way the brain links drugs to the environment is a really exciting part of this article,” said one of the authors, Hermina Nedelescu, Ph.D., a researcher at Scripps Research. “Once we can narrow down which chains in the brain are responsible for this learning related to care, we can start thinking about how to target them with therapeutic tools.”

The group is now planning future experiments to more specifically identify the exact groups of neurons involved.

IMAGE LOAN: Scripps Research