Brain circuit driving addictive behaviour identified

Section of a mouse brain showing in red the circuit that reinforces the behaviour, and in green the circuit that reinforces the decision to continue. If the green projection is very active, the mice self-stimulate their red projection despite negative consequences. They become compulsive. Vincent Pascoli/UNIGE

Researchers at the University of Geneva have pinpointed how the brains of mice susceptible to compulsive addiction are different from those of mice that are able to cease a rewarding behaviour when it comes with negative consequences.

It’s long been known that some people respond more compulsively to addictive drugs than others, continuing to consume them even long after the negative consequences of doing so outweigh the pleasures. Now, using mouse models, researchers at the University of Geneva (UNIGE) have observed the brain activity underlying this difference.

The scientists created a reward system for the mice in which a lever, when pulled by the animals, delivered laser light via an optical fibre implant, which in turn activated dopamine-releasing neurons. The release of the chemical dopamine is also associated with drug use and the development of addiction in humans.

After allowing the mice to get used to using the lever to activate their brains’ reward systems, the researchers introduced weak electric shocks to the feet of the mice at the same time as some of the lever-pulls. Following the introduction of the shocks, about 40% of the mice chose to pull the lever less often to avoid them, but some 60% carried on as before, willing to run the risk of punishment to continue stimulating their reward centres.

Next, the team measured the mice’s brain activity. They found that communication between a region of the brain involved in decision-making and a region involved in voluntary action was heightened in the “addicted” mice compared to those that stopped pulling the lever.

“We do not know why one person becomes addicted to drugs while another doesn’t, but our study identifies the difference in brain function between the two behaviours,” summarised Christian Lüscher, a professor in the UNIGE Departments of Basic and Clinical Neurosciences in a press release on Thursday. Lüscher is a senior author of a paper summarising the team’s results, which was published this week in the journal NatureExternal link.

Moreover, the researchers found that they were able to regulate the activity of the neurons connecting these regions, again using the laser light approach, cementing their conclusion that this was the brain circuit responsible for the compulsive behaviour they observed.

“When we reduced the activity of the circuit in an addicted mouse, it stopped activating the lever,” explained lead author Vincent Pascoli, a researcher in UNIGE’s Department of Basic Neurosciences. Likewise, increasing the circuit activity turned a previously controlled mouse into a compulsive one.

The breakthrough has helped identify a crucial “how” in the neurobiology of addiction, but the “why” – the reason some mice experience this strengthened brain activity and others do not – is a target for future research. Since the mice in this study were all genetically identical, one lead could be environmental influences that can alter an organism’s gene and brain function.

“Thanks to the present study, we now know which circuit causes the addiction. It will then be easier to find out what causes the disruption in the circuit,” Pascoli concluded.