Wisconsin’s affinity for alcohol — and the drug’s complicated cultural impact on the state — can in many ways be explained by a few straightforward biochemical processes. Alcohol’s effects on the human brain and nervous system, and the role genetics plays in how people metabolize the chemical, point to one important factor in its widespread use and abuse.

“At a fundamental level, I bet most people who drink [alcohol] don’t really know exactly how this drug works,” said Kevin Strang, a faculty associate in the Department of Kinesiology at the University of Wisconsin-Madison School of Education. “It’s unique in the drug world.”

Strang recounted the physiological effects of alcohol and their relationship with genetics for a June 22, 2015, lecture on the UW-Madison campus recorded for Wisconsin Public Television’s University Place.

Unlike other drugs, which target specific biological functions, the chemical composition of ethanol — the form of alcohol humans are able to readily metabolize and have consumed since the advent of agriculture — lends it the ability to act as a universal “skeleton key” and affect proteins throughout the human body, Strang said. It’s why alcohol broadly affects the body, including the cardiovascular, gastrointestinal, urinary, reproductive, endocrine and nervous systems.

Strang zeroed in on the effects of alcohol within the nervous system, and specifically how alcohol impacts the brain pathways of dopamine.

A neurotransmitter and hormone, dopamine has several functions in the body, one of which is central to arousing the brain’s pleasure center. For most people, alcohol consumption leads to a flood of dopamine into that part of the brain, producing a classic feeling of euphoria, or “buzz.”

“It turns out the way alcohol influences the dopamine pathway explains why binge drinking happens, and it also can explain why some people become dependent on alcohol for enjoyment,” Strang said.

Abuse behaviors emerge because alcohol not only leads to feelings of euphoria, but as it leaves a person’s system, dopamine levels crash. A typical man can metabolize one standard alcoholic drink (1.5 fluid ounces of distilled spirits or about 12 fluid ounces of beer) per hour, with a typical woman taking a little longer, meaning the fleeting buzz is followed by a period when falling dopamine levels reduce the feeling of pleasure. The only way to maintain a buzz is to consume more alcohol.

“As long as the rising phase [of dopamine] is maintained, the euphoria, the mood boost is maintained,” Strang said. The rise and fall of dopamine is connected with the concentration of alcohol in a beverage, he added, which is why a shot of liquor produces a quicker buzz and more speedy mood crash than a can of beer.

In addition to producing a classic buzz and post-drinking hangover, alcohol can inhibit memory formation, reduce social inhibitions and can increase anxiety, though Strang added that its effects vary. Excessive alcohol consumption can amplify these effects, sometimes leading to a complete inability to form new memories and risky behaviors.

Alcohol’s variable impacts on people are partly related to genetics, Strang said, pointing to several animal studies. These included one in which fruit flies were conditioned and bred to be particularly susceptible to the intoxicating effects of alcohol. Other studies showed that alcohol tolerance and an affinity for alcohol could be bred into animals, including mice and monkeys.

“Animals don’t like to drink alcohol usually, but if you can find a couple of animals that don’t mind it and crossbreed them and then take their offspring and find ones that don’t mind [alcohol] or even like it and crossbreed them, you can breed a love for drinking alcohol over water or fruit juice or anything else,” he said.

An inclination toward alcohol can also result from epigenetic processes, whereby life experiences alter gene expression. Strang pointed out controversial studies at UW-Madison (the Harry Harlow research) that showed, among other things, monkeys who were neglected during infancy were more likely to seek out alcohol than their well-cared for peers.

Most human civilizations have incorporated the consumption of alcohol into religious and social customs for thousands of years. During most of that history and in many places, including crowded and filthy medieval European cities, sterile alcohol was often a safer beverage to drink than water. Strang said this reality may have led to selective pressure that favored people who could tolerate or preferred regular alcohol consumption.

“Those who preferred alcohol to water and could handle its toxicity [would] survive more often and have more children,” he said. “Their genes [would] be passed along.”

Some of the descendants of these European city-dwellers eventually emigrated to Wisconsin.

“Who settled the upper Midwest? It was settlers from large cities in Europe where if you didn’t drink alcohol and if you weren’t good at drinking alcohol, you would’ve died of cholera or dysentery,” Strang said, using a bit of hyperbole to make the point that early immigration to Wisconsin brought a population accustomed to alcohol consumption.

That potential genetic preference, combined with over a century of cultural and economic development in which alcohol has played a central role in the state, has led to a population where alcohol is a deeply-seated force in life and death. One in 10 deaths among working-age adults in Wisconsin is attributable to alcohol, Strang noted, adding: “Wisconsin has a drinking problem.”

Key facts:

• Alcohol is the second-most consumed drug in the world, following caffeine.
• Ethanol — the form of alcohol humans consume — forms an “amphipathic” molecule, meaning it possesses both water-attracting (hydrophilic) and fat-attracting (lipophilic) properties. The molecular structure of ethanol makes it capable of interacting with proteins in many ways that are highly random, meaning it can affect the human body’s systems in all sorts of ways.
• Proteins that are very sensitive to the effects of alcohol are integral to the functioning of brain cells (neurons).
• Alcohol consumption triggers the production of the neurotransmitter dopamine, which floods the brain’s pleasure center and produces a euphoric feeling.
• Excessive alcohol consumption can lead to heart arrhythmias and attacks, cirrhosis of the liver, gastric ulcers, dehydration and irregular menstrual cycles, among many other physiological effects.
• Individuals who begin drinking early in life, by age 14, have a 50-50 chance of becoming alcohol dependent later in life, whereas individuals who wait until their early 20s to begin drinking have an 8% chance.
• Around 17% of U.S. adults binge drink, according to the Centers for Disease Control and Prevention.

Key quotes:

• On alcohol’s ability to affect systems throughout the human body: “[Alcohol is] unique in the drug world. When a pharmacologist designs a drug aimed at a brain protein or aimed at your kidney or your liver, they’re often massive molecules that are shaped very specifically to attach to certain targets chemically. As we’ll see, alcohol, it’s a skeleton key. It’s a universal key.”
• On how alcohol consumption is treated as a reward for the brain’s pleasure center: “This is real. This happens to most people who drink alcohol. So you have these pleasure centers in your brain that are there for a good reason. When you do something that increases the likelihood of your survival or your species’ survival, there’s a pleasure center in your brain that lights up. You get this great feeling that reinforces it. It says, ‘Do that again.’ So if you get a big bowl of fatty ice cream, this center lights up. ‘Do that again. You know, you’ll survive the next famine.’ Someone tells you they love you and they really mean it and you know they mean it, this pleasure center lights up. Interactions between people are really reinforced by this pleasure center and specifically dopamine.”
• On the importance of dopamine in the functioning of the brain: “Dopamine, it turns out, is a double-edged sword. Dopamine is a great thing. It lights up your pleasure center, it makes you feel good, but there are many disease conditions like schizophrenia, excess of dopamine is one of the underlying factors in people who have the mental disorder of schizophrenia.”
• On the demonstration that selective breeding can result in extraordinary alcohol-related behaviors in mice: “Well, this resistant strain of mice, they bred into their DNA, into their protein structure the ability to handle enormous amounts of alcohol, and they walk right across that bar and they don’t fall down.”
• On how alcohol’s pharmacological effects are much more variable than those of other drugs: “So Valium is a drug that you give to anyone on Earth, everyone has the same reaction. It’s a very specific, it’s an anxiolytic, it calms people down. It slows your brain down. Alcohol can do that but it can also do a lot of other things and it … affects so many different things, it’s sometimes been called a pharmacological hand grenade. Cocaine is a pharmacological scalpel. It really affects one thing. Alcohol affects a lot of things, and so the outcome can be very unpredictable.”

Editor’s note: The article was reported in collaboration with Wisconsin Public Radio for its “High Tolerance” series, which explores the state’s complicated relationship with alcohol.