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Mutant mice show new pathway in drug addiction

PARIS (AFP) - Scientists experimenting with genetically-modified mice said on Wednesday they had unveiled a molecular pathway that helps explain drug addiction and appetite.


The discovery focuses on the chemical process by which people become substance-dependent, according to the study, published by the British journal Nature.

Pleasure-giving drugs such as cocaine and heroine -- as well as food -- work by boosting levels of a messenger chemical called dopamine that stimulates the brain's "reward" centre.

But dopamine itself is only one part of a molecular cascade that leads to dependence.

Researchers led by Jean-Antoine Girault of the Pierre and Marie Curie University in Paris looked at a brain protein called DARPP-32 which helps the dopamine signalling process.

The team found that when lab mice were given a jolt of cocaine, amphetamine or morphine, DARPP-32 built up in part of the brain called the striatum.

They then created mice whose DNA had been modified so that the gene expressing DARPP-32 turned out a slightly altered form of this protein -- a form where just one amino acid building-block had been changed.

Mutant mice and wild mice were given two shots of cocaine or morphine seven days apart. The drugs had far less effect on the engineered mice, as shown in their movement, and these rodents were far less likely to crave another dose.

Just as interesting was the discovery that mutant mice trained to use their noses to poke a lever mechanism that delivered a food pellet were far less likely to push for the reward compared with their wild counterparts.

"Taken together these results show that (the) mutation... alters long-lasting responses to drugs of abuse, and decreases motivation for food reward," the study says.

Finding a pharmaceutical drug that can block the accumulation of DARPP-32 is a promising avenue for tackling addictions as well as certain kinds of mental illness in which dopamine is suspected to play a role.

Knowledge gained from this work could also help fine-tune treatment for Parkinson's disease, which is caused by dopamine depletion, France's National Institute for Health and Medical Research (Inserm) said in a press release.

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