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A Brain Network for Alcoholism?

A new study identifies brain network involved in compulsive alcohol drinking.

Alcoholism, also called AUD (alcohol use disorder) is a debilitating disorder that results in a wide range of mental and physiological health problems. On average, alcoholism reduces the life expectancy by 10 years. In the United States, about 88,000 people die from alcohol-related causes every year (National Institute on Alcohol Abuse and Alcoholism [NIAAA] Alcohol Facts and Statistics).

Despite the high public significance of AUD, it is still not well understood why some people develop AUD and others do not. According to the NIAAA, 86.3% of Americans aged over 18 years drank alcohol at some point in their life and 70.1% drank within the least year (NIAAA Alcohol Facts and Statistics). This shows that many people enjoy a cold beer or a glass of white wine every now and then. The vast majority of them, however, do not develop AUD. According to the NIAAA, the percentage of adults in the United States with AUD is 5.7% (NIAAA Alcohol Facts and Statistics).

A new neuroscience study published this week in the prestigious scientific journal Science now sheds light on a mechanism that could potentially explain why some people develop AUD but most do not (Siciliano et al., 2019). People do not developed AUD from one day to another. Typically, this is a gradual process, in which someone starts drinking alcohol casually like the majority of other peoples, but then gets into a habit of compulsive drinking. Compulsive drinking means that someone continues to drink alcohol, even though they face negative consequences, e.g., losing their jobs or partners. It is considered an important step in developing AUD.

In the study by Siciliano et al., (2019) the scientists investigated the neurobiology underlying compulsive alcohol drinking in mice. In the study, mice had to react to a tone in order to get access to alcohol. After some days, a bitter substance was added to the alcohol, making the taste experience very unpleasant. This way the scientists could observe which animals would drink large quantities of alcohol despite facing negative consequences. Like in humans, the mice showed large differences in their drinking habits. The scientists classified the mice into three groups:

· “low drinkers”: mice that did not drink much alcohol with or without the bitter taste

· “high drinkers”: mice that drank a lot of alcohol if it was not bitter, but reduced their drinking when they faced negative consequences

· “compulsive drinkers”: mice that drank a lot of alcohol no matter whether they faced negative consequences or not

The scientists than investigated a brain network between the cortex and the brainstem in order to identify whether it might explain why some mice show compulsive drinking while others do not. The two key brain structures involved in the network were the medial prefrontal cortex (mPFC) and the periaqueductal gray (PAG) in the brain stem. The mPFC is a cortical brain structure that controls avoidance of negative stimuli, e.g., it should initiate a reduction of alcohol consumption in the face of negative consequences. The PAG is involved in reaction to negative events and has been linked to how people react to alcohol withdrawal. These two brain areas are connected and the scientists hypothesized that functional deficits in this brain network could be a reason why some individuals develop a compulsive drinking habit but most do not. To test this hypothesis, they used cellular-resolution calcium imaging, a neuroscientific method to visualize brain activity in mice.

The results were quite striking: Even when the data from the first session in which the animals had not been classified into any group were analyzed, there was a strong difference between the “compulsive drinkers” and the “low drinkers” groups of mice. The “compulsive drinkers” showed more inhibitory responses in the mPFC-PAG network than the “low drinkers.” Thus, already in the early stages of the experiment the brain activity was predictive of whether an animal would later develop a compulsive drinking habit.

The scientists next used photoinhibition, a neuroscientific technique to inhibit activity of a specific brain network. They could show that if they inhibited the mPFC-PAG brain network, mice started to develop a compulsive drinking habit.

The scientists concluded that the mPFC-PAG brain network is crucial with regard to whether or not an animal developed a compulsive drinking habit. The higher inhibition of the network in the compulsive drinkers indicate that the normal function of this network to end behavior in the face of negative consequences is disrupted. This has important implications for understanding AUD in humans as it highlights the importance of further investigating this specific network in human patients suffering from AUD – hopefully contributing to the development of new and better treatment and prevention strategies in humans.


Siciliano CA, Noamany H, Chang CJ, Brown AR, Chen X, Leible D, Lee JJ, Wang J, Vernon AN, Vander Weele CM, Kimchi EY, Heiman M, Tye KM. (2019). A cortical-brainstem circuit predicts and governs compulsive alcohol drinking. Science, 366, 1008-1012.