'Brain circuit behind alcohol addiction in mice discovered'

Researchers have discovered the specific nerve cells in the brain behind reward-like behaviour linked to alcohol consumption and addiction, an advance that may lead to therapeutics to help people with alcohol use disorders.

The researchers, including those from the University of North Carolina (UNC) in the US, said a region of the brain called the central nucleus of the amygdala (CeA) plays a role in behaviours related to alcohol use and consumption.

However, they said, until now very little was known about the precise populations of brain cells, and their connections to other brain regions that mediate these behaviours.

In their study, published in the journal Neuroscience, the researchers pinpoint a specific neural circuit that when altered caused animal models to drink less alcohol.

"The fact that these neurons promote reward-like behaviour, that extremely low levels of alcohol consumption activate these cells, and that activation of these neurons drive alcohol drinking in animals without extensive prior drinking experience suggests that they may be important for early alcohol use and reward," said study senior author Zoe McElligott from UNC.

"It's our hope that by understanding the function of this circuit, we can better predict what happens in the brains of people who transition from casual alcohol use to subsequent abuse of alcohol, and the development of alcohol use disorders," McElligott said.

As part of the study, the researchers investigated a population of neurons which express a specific small protein -- neurotensin or NTS -- which contributes to reward-like behaviours associated with alcohol drinking.

McElligott was particularly interested in these neurons in the context of inexperienced alcohol use -- such as when a person first begins to drink alcohol.

The study noted that the NTS neurons are a subpopulation of other neurons in this CeA brain region which have been implicated in anxiety and fear.

The researchers found that selectively injuring the NTS neurons in the CeA -- while maintaining other types of CeA neurons -- caused male mice to drink less alcohol.

This manipulation did not alter anxiety-like behaviour, they said.

According to the researchers, this also did not affect the consumption of other palatable liquids such as sucrose, saccharin, and bitter quinine solutions.

"We found that these NTS neurons in the CeA send a strong projection to the hindbrain, where they inhibit the parabrachial nucleus, near the brainstem," McElligott said.

The scientists used a technique called optogenetics where light activates neurons.

When they stimulated the terminal projections of the CeA-NTS neurons in a brain region called the parabrachial, they found that it inhibited the nerve cells in this part.

The researchers said, light projection in this brain region with a laser, when the animal was in one half of its cage, caused them to spend more time in that space.

The mice also learned to perform a task to get the laser stimulation to turn on, and they would do this repeatedly, the scientists noted in the study.

Based on this observation, the researchers suggested that the mice found this stimulation to be rewarding.

"Furthermore, when we stimulated this projection, animals would drink more alcohol as compared to when they had an opportunity to drink alcohol without laser stimulation," McElligott said.

"In contrast to our study where we ablated the NTS neurons, laser stimulation of this parabrachial pathway also caused the animals to consume caloric and non-caloric sweetened beverages," she added.

When the animals were presented with regular food and a sweet treat, however, the researchers said the laser stimulation did not enhance the consumption regardless of their hunger state.

"This suggests that different circuits may regulate the consumption of rewarding fluids and solids," McElligott suggested.