Could this protein explain why drinking can be so pleasurable?

New research conducted in mice looks at how alcohol engages with the brain's reward center, and which mechanisms might be set in motion to prevent excessive drinking.

Catching up with friends and family over a glass of wine is a scenario familiar to many of us, yet alcohol consumption is often a divisive topic. It can be easy to get carried away and have one drink too many, which can sometimes have unwanted medical consequences.

Recently, Medical News Today have reported on many studies concerned with the effects of alcohol consumption, with some questioning how much alcohol is safe to drink and others suggesting that a couple of glasses may even be beneficial.


However, some people tend to engage in excessive drinking on a regular basis, and scientists are still struggling to understand the mechanism that leads to this excessive consumption.
Now, researchers from the University of California, San Francisco, led by Dr. Dorit Ron, have used mouse models to study what happens in the brain when alcohol is consumed preferentially.

It is known that mice, if given alcohol, might eventually begin to prefer it to other beverages, leading to a pattern of excessive drinking. This allowed the scientists to study the effect of heavy alcohol consumption on the central nervous system and identify the changes that take place in the brain.

"There is - rightfully - a lot of media attention right now on opiate abuse and addiction. But alcohol abuse and addiction are much bigger problems, and the human cost is staggering: 3.3 million people die every year in the world from alcohol abuse," explains Dr. Ron.

"Unfortunately, there are only a few medications on the market to reduce craving and relapse, and none of them work very well," she says.

Protein complex boosts excessive drinking

Research previously conducted by Dr. Ron and other colleagues pointed to a protein complex called mTORC1, which regulates protein synthesis, as playing a key role in substance abuse - including heavy drinking.

Previous studies suggested that drinking too much alcohol stimulates mTORC1 activity in a part of the brain known as the nucleus accumbens, which plays a key role in the reward circuit. They also suggested that the increased mTORC1 may be responsible for changes in this brain region that boost desire for alcohol, thus correlating with alcohol-seeking behavior.

The activity of mTORC1 can be suppressed using rapamycin, which is a compound with immunosuppressant properties. When researchers administered rapamycin to mice who had learned to seek alcohol, the animals' preference for alcohol was significantly reduced. Moreover, their taste for sugar water - a beverage that mice naturally find rewarding - was not diminished.

But the researchers were interested in finding out whether any drugs could be used to curtail the craving for alcohol in human adults with a propensity for heavy drinking. Rapamycin, they noted, has many side effects, so using it to target heavy drinking in humans should be avoided.

Protein responsible for brain changes

Dr. Ron's team went one step further with the current study and used RNA sequencing, a technique that allowed them to focus on mTORC1's role in protein synthesis and track the proteins associated with it, to better understand the mechanism that leads to excessive alcohol consumption.

The researchers found a link between mTORC1 and 12 different proteins but decided to target only one: prosapip1, a newly discovered protein that previous studies suggest is somehow involved with the synapses. Its function, however, remains unclear.

Dr. Ron and her team found that prosapip1 is responsible for the structural changes that take place in the nucleus accumbens following heavy drinking over a long period of time.

The team also wanted to see what would happen if the production of this protein was genetically inhibited. They observed that, in this situation, fewer brain changes that dictated alcohol-seeking behavior took place following heavy alcohol consumption.

Also, given the choice between alcohol and water, the mice involved in the experiment preferred water more often than alcohol. Once more, the mice's taste for sugar water was not impacted.

"We have identified a new protein that plays a crucial role in changing the landscape of neurons in the nucleus accumbens, which then leads to escalation of problem drinking. These findings open up research into the protein's role in neural plasticity, and also into how alcohol and other drugs of abuse alter our brains."  - Dr. Dorit Ron

The scientists hope that these findings will pave the way for research into novel treatments not just for alcohol abuse but also for other substance abuse disorders.

"I've been doing research on the molecular neurobiology of alcohol abuse for many years and this is the first time I've seen a signaling molecule that appears to be shared by many drugs of abuse. I think in a way this may be a gateway to understanding drug addiction - it's a very exciting time,"concludes

Dr. Ron.