During the holiday season, some people are teetotalers, while others imbibe with beer, a glass of wine, or a shot of pure, distilled spirits. While body size, sex, gender, and the number of drinks consumed influence how drunk someone gets, individual reactions to alcohol can also vary due to differences in genetics and tolerance.¹

Alcohol is broken down in the human body by two main enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Mutations in these enzymes alter alcohol metabolism; for instance, low ALDH activity can lead to metabolite buildup, causing face flushing and nausea. Beyond metabolism, other factors can also impact how alcohol affects coordination and drinking behavior. 

For instance, researchers found that family history of alcoholism can influence static ataxia or body sway symptoms after alcohol consumption: Those with a family history swayed less than those without.² This behavioral complexity led David Rossi, a molecular neuroscientist at Washington State University, to explore the brain as static ataxia involves the cerebellum, the brain region involved in motor function and balance. 

Alcohol suppresses excitatory signals while enhancing gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. When GABA receptors are stimulated, they reduce neuron firing, leading to sluggish movement.³ This wobbly effect isn’t limited to humans; Rossi found that rodents exhibit similar behavior.

He tested rodents’ motor skills on a spinning rod, comparing those with higher ADH and ALDH activity and a greater thirst for alcohol to less tolerant rodents. He found that their cerebellar GABA receptors varied in sensitivity.⁴ He noted, “The [rodents] that really like to drink are very insensitive to the motor impairing effects of alcohol.” These mice could keep drinking and maintain balance. Meanwhile, the lightweight mice felt the drunk-like effects of alcohol more easily and tumbled off. 

Tolerance also plays a key role. After a mouse’s equivalent of a weekend bender, as they withdraw, the cerebellum adjusts to alcohol’s inhibitory effects. Rossi remarked that repeated consumption leads to the brain downregulating inhibition, enabling rodents to stay functional even past their limit.

So, whether you’re a lightweight or a seasoned drinker, everyone’s response to alcohol is a varying mixture of environmental and genetic influences. Just remember, moderation is key!

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