17 Jul Gene Deficit May Give Immunity to Effects of Cocaine
MedicalResearch.com Interview with:
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Drug addiction is a chronically relapsing neuropsychiatric disease that affects 15.5 million people in Europe at a cost of 65.7 billion euros per year. All addictive drugs have in common to cause an artificial increase in the release of a neurotransmitter called dopamine, a very basic effect that can be found in all studied animal species from the fly to the man. The release of dopamine takes place in a region of the brain called the ventral striatum, or Nucleus Accumbens (NAc), which is directly involved in reward and reinforcement processes. An excess of dopamine release by the dopaminergic neurons projecting to the NAc from the Ventral Tegmental Area (VTA) triggers long-term changes in the brain, which can lead to addiction.
Cocaine is a prototypical addictive drug, since it is heavely abused in Western societies and extensively studied in animal models as well as humans.
We discovered that mice lacking the Maged1 gene showed a marked decrease in cocaine-elicited release of dopamine in the NAc and were entirely unresponsive to cocaine at behavioral level. In fact, they did not show any behavioral reaction normally observed after cocaine treatment, such as cocaine-elicited hyperlocomotion, sensitization (an increased effect of the drug following repeated administrations) or addictive behaviors, such as increased preference for places where the animal expects to obtain a cocaine reward or cocaine self-administration.
In a subsequent set of experiments, the researchers tried to identify what brain regions are responsible for Maged1 influence on cocaine effects and found that Maged1 expression is specifically required in the prefrontal cortex, and not in the neurons producing dopamine in the VTA, for the development of cocaine sensitization and dopamine release.
MedicalResearch.com: What should readers take away from your report?
Response: Very few genes are known to induce a complete lack of behavioral response to cocaine. Other members of this small group are established components of the reward system. Thus, Maged1 is a promising new entry point for the comprehension of the molecular mechanisms underlying drug addiction.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: We are now deciphering the specific molecular mechanisms through which Maged1 can exert this key effect in drug addiction with the aim of identifying potential targets for pharmacological treatments.
Citation:
Deletion of Maged1 in mice abolishes locomotor and reinforcing effects of cocaine
Jean‐François De Backer, Stéphanie Monlezun, Bérangère Detraux, Adeline Gazan, Laura Vanopdenbosch, Julian Cheron, Giuseppe Cannazza, Sébastien Valverde, Lídia Cantacorps, Mérie Nassar, Laurent Venance, Olga Valverde, Philippe Faure, Michele Zoli, Olivier De Backer, David Gall, Serge N Schiffmann, Alban de Kerchove d’Exaerde
DOI 10.15252/embr.201745089| Published online 12.07.2018
EMBO reports (2018) e45089
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Last Updated on July 17, 2018 by Marie Benz MD FAAD