Alcohol triggers unique activity in amygdala neurons

A study on mice identified a group of neurons in the central amygdala region of the brain that display a unique pattern of increased activity during voluntary alcohol consumption. While these neurons also responded to other fluids, their activity was significantly higher when mice drank alcohol compared to when they drank sucrose or water. This unique response did not diminish over time. The paper was published in Progress in Neuro-Psychopharmacology and Biological Psychiatry.

Alcohol use disorder is a chronic condition characterized by a problematic pattern of alcohol consumption that leads to significant distress or impairment in daily functioning. Despite treatment, relapses are frequent. Estimates suggest that around 30 million people in the U.S. alone are affected by it, which is around 9% of the population.

People with alcohol use disorder tend to have difficulty controlling how much they drink or how often they drink. They tend to continue drinking despite negative consequences. Common symptoms of this disorder include tolerance, withdrawal symptoms, and spending a great deal of time obtaining, using, or recovering from alcohol.

Excessive alcohol drinking, characteristic of alcohol use disorder, increases the risk of liver disease, cardiovascular problems, and certain cancers. It also has substantial psychological and social consequences, including depression, anxiety, family conflict, and work-related difficulties.

Study author Christina L. Lebonville and her colleagues note that studies of rodents have revealed that the central amygdala is a key region of the brain for alcohol drinking behaviors, particularly in alcohol dependence. This region contains three groups of neurons (sub-nuclei) that differ in the type of neuropeptide they express.

Neuropeptides are small protein-like molecules that neurons use to communicate with each other and to regulate various functions of the body. Unlike neurotransmitters, neuropeptides are released more slowly and they act over a longer time span.

One of these groups of neurons produces dynorphin, a neuropeptide involved in stress, pain, and negative emotional states. They are called dynorphin-expressing neurons or CeADyn neurons.

Previous studies implicated their activity in excessive alcohol drinking both during acute and chronic alcohol exposure. They also showed that CeADyn neurons regulate both binge alcohol drinking and drinking enhanced by stress in individuals with alcohol dependence. The disruption of their activity reduced alcohol drinking.

This study was conducted on 35 prodynorphin-Cre mice. These are genetically engineered mice with genetic properties that allow researchers to selectively label, monitor, and manipulate their CeADyn neurons. Mice were 8–17 weeks of age at the start of the experiment. They had free access to food throughout the experiment and free access to water outside experimental drinking sessions.

The study authors performed a surgery on these mice during which they injected a virus into their central amygdala. This virus changed their DNA so that a fluorescent calcium sensor was expressed in their CeADyn neurons, allowing the authors to measure their activity. At the same time, they implanted a small optical fiber above this region allowing them to record neural activity through light signals (fiber photometry).

After recovery from surgery, mice were given access to different solutions for 2 hours per day, 5–6 days per week. In the first experiment, mice had access to 20% alcohol for 3 weeks, water for two weeks, and 0.5% sucrose for three weeks.

In the second experiment, mice first had access to solutions with different quinine concentrations, followed by water, water after 24 hours of water deprivation, a combination of 0.5% sucrose and low quinine concentrations, and 0.5% sucrose with high quinine concentrations. The study authors recorded the brain activity of the mice during these periods.

Results showed strong increases in CeADyn neuron activity after bouts of alcohol drinking compared to sucrose or water drinking. Behaviors specific for drinking alcohol, such as longer bout durations, did not fully explain the differences in the pattern of activity of these neurons when mice were drinking alcohol compared to when they were drinking something else.

“No other conditions or solutions tested reproduced the pronounced change in CeADyn activity associated with alcohol drinking. These findings support the presence of a unique functional signature for alcohol in a cell population known to control excessive alcohol drinking and further advance fiber photometric normalization and analytical methods,” the study authors concluded.

The study contributes to the scientific understanding of the neural underpinnings of alcohol drinking behaviors. However, it should be noted that this study was done on mice, not on humans. While humans and mice share many physiological characteristics, they are still very different species. Findings on humans may differ.

The paper, “Alcohol drinking is associated with greater calcium activity in mouse central amygdala dynorphin-expressing neurons,” was authored by Christina L. Lebonville, Jennifer A. Rinker, Krysten O’Hara, Christopher S. McMahan, Michaela Hoffman, Howard C. Becker, and Patrick J. Mulholland.