Drugs: the circuit of the addiction identified

Cross-section of a mouse brain showing in red the circuit that reinforces the be

Cross-section of a mouse brain showing in red the circuit that reinforces the behavior, in green the circuit that makes the decision to continue. If the green projection is very active, the mice self-stimulate their red projection in response to negative consequences. They become compulsive. UNIGE

What happens in the brain of a person who uses drugs compulsively - Researchers at the UNIGE have identified the brain circuit that controls this addictive behavior.

What happens in the brain of a person who uses drugs compulsively - Does this function differently in a person who uses drugs in a controlled way?To solve this enigma, neurobiologists from the University of Geneva (UNIGE) have studied the differences in brain function between these two categories. They discovered that in compulsive users, the brain circuit linking the decision-making area to the reward system is reinforced. In a model of addiction in mice, they also found that by decreasing the activity of this circuit, compulsive mice were able to manage themselves and that conversely, by stimulating it, a mouse that initially lost control became addicted. This major discovery can be read in the journal Nature .

Addiction is a disease that evolves in stages: first the first exposure to the substance, then the controlled use, and finally the compulsive use that pushes the person to take an addictive substance despite many negative effects on his or her life (debts, social isolation, prison, etc.). According to clinical estimates, only one person in five moves from controlled to compulsive use. Why is this?

Today, we still do not know why one person becomes addicted to drugs while another does not, but thanks to this study, we know what the differences are in terms of brain function between these two categories," enthuses Christian Lüscher, professor in the Department of Basic Neurosciences at the Faculty of Medicine and researcher in the Department of Clinical Neurosciences at the University Hospitals of Geneva (HUG).Christian Lüscher, a professor in the Department of Basic Neurosciences at the Faculty of Medicine and a researcher in the Department of Clinical Neurosciences at the University Hospitals of Geneva (HUG). But be careful not to confuse addiction with dependence, he warns. Dependence means that a withdrawal will be necessary, but it does not necessarily lead to an addiction, i.e. the compulsive need to consume. For example, everyone becomes addicted to heroin after the first injections, but not everyone uses it uncontrollably.

Negative effects are no match for addiction

In order to identify differences in brain function, researchers allowed mice to stimulate their reward system, located deep in the brain stem, by pressing a small lever. This is the area that is activated by drug use and causes pleasure. The mice quickly understood how this worked and used the lever extensively. This is the equivalent of controlled consumption in people. In order to be able to observe which mice will sink into compulsive consumption, a negative effect must be introduced when stimulating their reward system, explains Vincent Pascoli, researcher at the Department of Basic Neurosciences at the UNIGE Faculty of Medicine and first author of the study. Here, the mice received a mild electric shock when they operated the lever. Quickly, 40% of the mice stopped activating the lever, following the introduction of the punishment. But 60% continued to stimulate their reward system, ignoring the negative consequence.

Thanks to a new technique that allows us to measure activity in the brain live, we have discovered a circuit that is much more active in the addicted mice than in the controlled consumption mice," says Christian Lüscher. This circuit extends from the orbitofrontal cortex to the dorsal striatum, located in the basal ganglia of the reward system, and targets this reward system. The orbitofrontal cortex, just above the eyes, is responsible for decision making.

The addiction circuit can be modulated

In order to verify that this circuit is indeed responsible for compulsive behavior, neurobiologists at the UNIGE artificially increased the activity of this circuit in a mouse controlling the stimulation of its reward system. The mouse quickly became addicted, adopting a compulsive behavior. Conversely, we decreased the activity of the circuit in an addicted mouse, and it stopped activating the lever," says Vincent Pascoli.

The mice studied in this experiment are all genetically identical. So why is the activity of this brain circuit not the same for all of them - This is THE question we will try to answer in our future research, confirms Christian Lüscher. Several hypotheses have been formulated, such as epigenetic contributions based on life experiences that make each living being unique and influence the functioning of its genes and brain. Thanks to this study, we know which circuit causes addiction. It will then be easier to discover what causes the disruption of this circuit, concludes Vincent Pascoli.


December 20, 2018

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