Brain discovery could change the way we treat alcohol dependence forever

Drinking alcohol is an individual choice with varying effects. Some people can consume alcohol every day and never develop any dependence, while less frequent drinking can cause others to become addicted.

For years, scientists have been puzzled as to why people with similar backgrounds and health characteristics can have starkly different responses to alcohol. In a recent study, researchers announce it may have something to do with how alcohol preferences are manifested in the brain.

In the experiment, rats who preferred alcohol had higher levels of brain activity in the orbitofrontal cortex (OFC) when they consumed it. The OFC is a brain region associated with impulsivity, reward, and decision-making. Meanwhile, rats who didn't like alcohol as much exhibited lower activity in the OFC.

These results suggest that neuronal activity in the brain's OFC can encode alcohol preferences. In turn, those preferences can influence drinking behavior.

This finding was published Monday in the journal eNeuro.

Study co-author David Moorman is a behavioral neuroscientist at the University of Massachusetts, Amherst. He tells Inverse that certain systems in the brain, like the OFC, become "differentially engaged depending on how much or little one likes alcohol."

Although the study was conducted in rats, the findings may lead to major breakthroughs in treating alcohol use disorder (AUD) in humans, Moorman says.

"There are, of course, lots of reasons why people drink different amounts of alcohol," Moorman explains. "But if this preference is somehow encoded in the OFC, we might be able to use OFC activation as a biomarker for the potential of an individual to develop alcohol use disorder (AUD)."

The study — To explore how alcohol preferences manifest in the brain, researchers recorded rat's brain activity while they sought and consumed alcohol and sugar substances freely in the lab. They also analyzed how the rats' preferences for alcohol correlated with brain activity.

The team offered intermittent access to 20 percent ethanol solutions to rats for a month. Then, they trained rats to self-administer ethanol (both 10 and 20 percent solutions) and sucrose (15 percent) — a sugary reward that all rats enjoy — and observed their patterns of consumption.

Throughout the rats' ethanol and sucrose consumption, researchers measured the activity of neurons in the OFC, a region that's previously been linked to reward motivation and drug use.

The rats were then subdivided into high or low ethanol drinkers based on how much they consumed in their cage and how much they sought out the 20 percent ethanol solution.

Across the board, rats were equally motivated to consume the 10 percent ethanol solution and sucrose. But, overall, how each rat brain reacted to each offering varied based on their alcohol preference.

Activity in the OFC spiked when high ethanol drinkers consumed alcohol, similarly to how the OFC was activated when they got sucrose. Meanwhile, the consumption of low ethanol solutions was linked to lower levels of OFC activation in response to alcohol compared to sucrose.

The strength of this OFC activation was directly linked to how much the rats preferred drinking 20 percent ethanol. This suggests that OFC neuronal activity encodes individual preferences for alcohol.

"We think we’re capturing some marker of innate preference that could potentially predict the development of AUD," Moorman says.

Looking forward — In the far future, researchers may also be able to target OFC function and reduce alcohol preference. This could help people with AUD if done right, but it would be a considerable challenge.

"We have to be very careful to only influence high alcohol preference and not, for example, all types of pleasure or motivation, aspects of which are also encoded in the OFC," Moorman explains. "Turning off OFC might be challenging in humans, particularly if we only want to turn off alcohol-related parts of OFC. Knowing where to look is an important first step."

Further research in humans is needed to determine if these findings translate exactly to people. Scientists haven't yet pinned down the root developmental, environmental, and genetic causes driving these preferences.

For now, rats offer a more controlled experimental setting to isolate the underlying mechanisms and untangle these complex factors.

"Although alcohol and drug dependence is a very human disease, and stems from the interaction between biological and environmental factors, understanding the underlying mechanisms in a very controlled system has the potential to precisely target what’s happening when people have problems controlling their alcohol intake," Moorman explains.

"It can seem like a long road from rats or mice drinking alcohol to treating people with AUD, but we hope that our work adds to the collective knowledge base that can (hopefully sooner rather than later) be translated into treatments."

Abstract: Orbitofrontal cortex (OFC) plays a key role in representation and regulation of reward value, preference, and seeking. OFC function is disrupted in drug use and dependence, but its specific role in alcohol use disorders has not been thoroughly studied. In alcohol-dependent humans OFC activity is increased by alcohol cue presentation. Ethanol also alters OFC neuron excitability in vitro, and OFC manipulation influences ethanol seeking and drinking in rodents. To understand the relationship between OFC function and individual alcohol use, we recorded OFC neuron activity in rats during ethanol self-administration, characterizing the neural correlates of individual preference for alcohol. After 1 month of intermittent access to 20% ethanol, male. Long-Evans rats were trained to self-administer 20% ethanol, 10% ethanol, and 15% sucrose. OFC neuronal activity was recorded and associated with task performance and ethanol preference. Rats segregated into high and low ethanol drinkers based on homecage consumption and operant seeking of 20% ethanol. Motivation for 10% ethanol and sucrose was equally high in both groups. OFC neuronal activity was robustly increased or decreased during sucrose and ethanol seeking and consumption, and strength of changes in OFC activity was directly associated with individual preference for 20% ethanol. Ethanol-associated OFC activity was more similar to sucrose-associated activity in high vs. low ethanol drinkers. The results show that OFC neurons are activated during alcohol seeking based on individual preference, supporting this brain region as a potential substrate for alcohol motivation that may be dysregulated in alcohol misuse.