A deficit in dopamine in a region of the brain involved in motivation is associated with alcohol dependence, and correcting this abnormality can reduce addiction. That’s what a team Inserm of the Institute of Neurosciences of Grenoble has just demonstrated, in rats. The researchers are thus opening up a new, welcome therapeutic avenue in an attempt to effectively treat this disorder, which represents a major public health problem.
In France, about 90% of adults are regularly exposed to alcohol and nearly a quarter consume too much, ie more than two glasses a day and almost every day. The main risk of this excessive consumption is addiction: it is manifested by a compulsive need to drink despite negative consequences on one’s health, personal and professional life, as well as by psychological and physical suffering in the event of lack. But not all heavy drinkers become addicted, only a fraction of them develop this disorder. However, the reasons and mechanisms of this vulnerability remain poorly understood.
At the Grenoble Institute of Neurosciences, Sébastien Carnicella’s team is seeking to find out more thanks to its expertise on the brain circuits of motivation that involve dopamine. ” Ce neurotransmitter participates in the desire to do something, via the reward it provides. For example, dopamine levels are increased when an individual consumes alcohol for pleasure. But the effect of this neurotransmitter in the phenomenon of addiction is not clear. It is assumed that it plays a role, but so far drugs that inhibit its action have not shown efficacy. “, explains Sébastien Carnicella.
End of debate
The researcher and his team analyzed the dopamine level in alcohol-dependent rats, in a region of the brain involved in motivation: the nigrostriatal pathway. Specifically, a group of rats was repeatedly exposed to alcohol. Some developed addictive behavior, that is, they could not stop drinking it even when the consumption was associated with the triggering of an unpleasant stimulation. In these animals, the researchers found a dopamine deficiency in the nigrostriatal region. Secondly, the team of scientists selected rats that had not developed addiction despite their exposure to alcohol (the unpleasant stimulation caused them to give up taking alcohol). The researchers lowered their dopamine levels in the nigrostriatal region so that the concentration of the neurotransmitter was similar to that observed in animals who had become dependent. As a result, these rats also eventually became addicted. ” These experiments prove the involvement of a dopamine deficit in addiction, while it was previously debated », emphasizes Sébastien Carnicella.
This discovery prompted his team to test a therapeutic avenue: by using a pharmacological substance that stimulates the production of dopamine in the brain, the researchers managed to reduce the animals’ dependence on alcohol. ” It’s about a proof of concept. In animals, the increase in the level of dopamine makes it possible to fight against this addiction. We must now test this therapeutic avenue in humans, knowing that the safety profile of the molecule we used has already been validated in previous clinical studies. »
A role in all addictions?
However, questions persist at the end of this work, in particular on vulnerability to alcohol. ” Why within a group of rats exposed in the same way to alcohol, some became dependent and others not? We still don’t know the answer to this question. In particular, we need to check whether the dopamine level in the nigrostriatal region is lower in dependent animals even before their exposure to alcohol. We will also study the genetic and epigenetic aspects related to the production of this neurotransmitter, as well as its effect on the neurons on which it acts. Ultimately, better knowledge of the circuits involved could have an impact on our understanding of all addictions. Some studies already suggest the existence of anomalies linked to the activity of dopamine in other types of addiction, such as cocaine addiction. concludes Sébastien Carnicella.
Alcohol: benchmarks to limit the risks
If there is no threshold below which the consumption of alcohol is without danger to our health, scientific knowledge makes it possible to define benchmarks which limit the risks incurred.
Updated in 2017, these benchmarks recommend:
- do not consume more than 10 glasses of alcohol per week
- do not consume more than 2 glasses per day
- do not drink alcohol at least 2 days a week
Sébastien Carnicella is head of the Physiopathology of Motivation team at the Grenoble Institute of Neurosciences (GIN, Inserm unit 1216/Grenoble Alpes University, Grenoble).
Source : R Goutaudier et al. Hypodopaminergic state of the nigrostriatal drives compulsive alcohol use pathway. Molecular Psychiatry, online edition November 14, 2022. doi: 10.1038/s41380-022–01848‑5