Male Mice Seek Alcohol When Isolated, Females Show Opposite Trend: "Men and Women Use Different Neural Strategies When Lonely"

Northwestern University and Salk Institute Teams Conduct Experiment
Male Mice Living in Isolation Reach Peak Alcohol Intake Within Seven Days
Artificial Activation of Brain Circuit Increases Drinking, While Suppression Decreases It

A study has found that male mice who spend longer periods alone tend to drink more alcohol.

Image to aid article understanding. Pixabay

According to Yonhap News on August 26, a research team from Northwestern University and the Salk Institute for Biological Studies in the United States published a paper in the scientific journal Nature Neuroscience reporting that social isolation alters a specific brain circuit in male mice and increases their alcohol consumption. The circuit in question acts as a pathway connecting the brain region that processes emotions with the area responsible for judgment.

Social isolation is increasing worldwide and is considered a major public health risk factor. In 2023, then-U.S. Surgeon General Vivek Murthy warned that loneliness and social isolation had reached epidemic levels. While mounting evidence shows a strong association with substance misuse, including alcohol and drugs, the specific mechanism by which isolation changes the brain to increase alcohol-seeking behavior had not been clarified.

To investigate, the research team kept groups of adult mice together and then separated some to live alone, thereby creating an experimental model of social isolation. Each day, the mice could choose to drink either water or a 15% alcohol solution for one hour. After observing the mice over 11 days, markedly different patterns emerged depending on sex. Among males, the longer they were isolated, the greater their alcohol consumption became, reaching its highest level after one week and then maintaining that level. Conversely, females actually drank less alcohol as the period of isolation increased. Water consumption did not change in either group.

Brain Circuit Altered by Isolation Controls Alcohol Consumption in Male Mice

To see how these differences manifested in the brain, the researchers used miniature microscopes to observe neural activity at the moment the mice chose whether to drink alcohol. They focused on neurons projecting from the basolateral amygdala to the medial prefrontal cortex—the former processes emotions, stress, and social information, while the latter is involved in reward, motivation, and behavioral control.

They found that, in males, social isolation increased the excitability of this circuit, while in females, it decreased it. The more active the circuit became in males, the greater their alcohol consumption. At the cellular level, these neurons responded differently when drinking water versus alcohol, and the stronger the response to alcohol, the more frequently the mice drank.

The team also investigated whether this brain circuit is a cause or result of alcohol drinking. Using optogenetics, a technique that can turn brain circuits on or off with light, they artificially activated the circuit in socially housed males and observed an increase in alcohol consumption. In contrast, when they suppressed the circuit in isolated males, drinking frequency decreased. The researchers concluded, "Social isolation reshapes the brain to respond more strongly to alcohol cues by altering how the prefrontal cortex processes reward information."

"Men and Women Rely on Different Neural Strategies When Lonely"

The reason for the opposite results based on sex has not yet been determined. Risha Patel, assistant professor at Northwestern University Feinberg School of Medicine and first author of the paper, said, "We cannot definitively say why isolation increases alcohol consumption in males but decreases it in females," but added that "the sex difference observed here overlaps with trends reported in several human studies." She went on to state, "It turns out that men and women depend on different neural strategies when lonely. This may help explain the long-noted sex differences in neuropsychiatric disorders."

However, the team emphasized that, since the study was conducted on mice, additional research is needed to determine if similar effects occur in humans. The findings do not prove that loneliness directly leads to alcohol consumption in people.

The next step for the researchers is to investigate why this circuit remains hyperactive during isolation and how other brain regions, including the medial prefrontal cortex, are involved. They also plan to determine whether hormones or structural brain differences are responsible for the sex-specific responses.

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