Milan D Valyear – Concordia University
Milan D. Valyear, Iulia Glovaci, Audrey Zaari, Soraya Lahlou, Ivan Trujillo-Pisanty, C. Andrew Chapman & Nadia Chaudhri (2020) Dissociable mesolimbic dopamine circuits control responding triggered by alcohol-predictive discrete cues and contexts. Nature Communications 11:1–14.
Identification of two separate neuron circuits as targets for treating alcohol use disorder
Alcohol misuse accounts for 1.9% of yearly deaths in Canada. The dopamine system in the brain has been hypothesized to play an important role in alcohol misuse, however relapse rates are high and dopamine-targeted medications are unsuccessful at treating alcohol relapse. Dr. Milan Valyear and colleagues demonstrate in this study that discrete alcohol cues (such as the sight of a beer) and alcohol contexts (like the ambiance of a bar), when presented in combination, are powerful triggers for relapse-like behaviour in rats. They also discovered that signals in the brain that are important for controlling behaviour in response to discrete cues and context arise from separate projections of dopamine neurons.
The researchers found that the capacity for different types of environmental stimuli to serve as alcohol cues and instigate alcohol-seeking behaviour required the activity of separate dopamine projections. Specifically, they showed that rats exhibit more alcohol-seeking behaviour in response to a discrete cue when that cue is presented in an alcohol context wherein they had consumed alcohol before, compared to a neutral context wherein alcohol was never available. Using cutting-edge neuroscience tools, they shut down two separate populations of dopamine neurons that project from the midbrain (ventral tegmental area) to different areas of the ventral striatum (accumbens core or shell). Shutting down one projection (core) reduced alcohol-seeking behaviour in response to the discrete cue in both contexts, whereas shutting down the other projection (shell) reduced alcohol-seeking behaviour in response to the discrete cue only in the alcohol context. Together, these findings demonstrated for the first time that a context could elevate alcohol-seeking in response to a discrete cue and that the influence of contexts and discrete cues over behaviour was controlled by separate dopamine projections.
The finding that these discrete cues and contexts interact to elevate relapse-like behaviour suggests that when sober people encounter a discrete alcohol cue in an alcohol context, for example when they are offered a beer in a bar, that it may be particularly difficult to refuse that offer compared to being offered an alcoholic beverage in a different context, like at work. Clinicians treating alcohol misuse in people should be mindful of contexts that are powerful relapse-triggers for their patients and implement strategies to address these triggers. The finding that the dopamine system plays two distinct roles in relapse-like behaviour has implications for the development of medications to treat alcohol misuse. Existing medications that target the dopamine system may be ineffective because they incidentally target multiple components of the dopamine system. The work by Dr. Milan Valyear and colleagues suggests that medications should be developed that target separate dopamine projections, and that these medications may be effective at treating alcohol use disorder.
Dr. Milan D Valyear
This project, which was also awarded the Annual Jane Stewart Prize, formed the foundation of Milan Valyear’s doctoral thesis in the laboratory of Dr. Nadia Chaudhri at Concordia University. Although Dr. Valyear was responsible for virtually every aspect of this project, he credits Dr. Chaudhri’s mentorship as critical for the success of the project and for shaping him as a person and scientist. Dr. Valyear is particularly proud to have combined Pavlovian conditioning, pharmacology, immunohistochemistry, confocal microscopy, microdialysis, electrophysiology, and chemogenetic techniques in transgenic rats to answer important questions about the neurobiological and behavioural basis of alcohol misuse.
In addition to the traditional work required to produce a scientific manuscript, Dr. Valyear made a concerted effort to communicate the findings of this project to the scientific community and general public. He presented this work as a speaker and poster presenter at a premier research conference in his field, the Gordon Research Conference on Alcohol, where he received best poster award. He wrote an opinion piece that was published in the Montréal Gazette about the contribution of context to relapse. He also competed in the 3-minute thesis competition where he spoke to a large public audience and won first place. It is a personal goal of his to disseminate all his scientific findings within and beyond the scientific community.
Dr. Valyear is currently a post-doctoral fellow in Dr. Jonathan Britt’s laboratory at McGill University where he is studying how dopaminergic and glutamatergic inputs to the ventral striatum contribute to valence and salience processing, which are two psychological processes that are often disrupted in psychopathology. Dr. Valyear hopes to understand how the activity of cells within, and inputs to, the ventral striatum determine salience and valence to inform the development of interventions that restore appropriate functioning and treat psychopathology.
Dr. Valyear encourages those who are able to donate to the Wingspan Award which was recently launched by his PhD supervisor Dr. Chaudhri and aims to support the training of neuroscientists from underrepresented groups.
This work was supported by grants from the Canadian Institutes of Health Research, the Fonds de recherche du Québec – Santé, the Canadian Foundation for Innovation, the Natural Sciences and Engineering Research Council and Concordia University.