Scientists have discovered a molecular process in the brain
triggered by cocaine use that could provide a target for treatments to prevent
or reverse addiction to the drug.
Reporting in the Journal
of Neuroscience, Michigan State University neuroscientist A.J. Robison and
colleagues say cocaine alters the nucleus accumbens, the brain’s pleasure centre
that responds to stimuli such as food, sex and drugs.
“Understanding what happens molecularly to this brain region
during long-term exposure to drugs might give us insight into how addiction
occurs,” said Robison, assistant professor in the Department of Physiology and
the Neuroscience Program.
What the study found
The researchers found that cocaine causes cells in the
nucleus accumbens to boost production of two proteins, one associated with
addiction and the other related to learning. The proteins have a reciprocal
relationship – they increase each other’s production and stability in the cells
– so the result is a snowball effect that Robison calls a feed-forward loop.
Robison and colleagues demonstrated that loop’s essential
role in cocaine responses by manipulating the process in rodents. They found
that raising production of the protein linked to addiction made animals behave
as if they were exposed to cocaine even when they weren’t. They also were able
to break the loop, disrupting rodents’ response to cocaine by preventing the
function of the learning protein.
“At every level that we study, interrupting this loop
disrupts the process that seems to occur with long-term exposure to drugs,”
said Robison, who conducted the study as a postdoctoral fellow at Mount Sinai
School of Medicine in New York City before joining the faculty at MSU.
Robison said the study was particularly compelling because
it found signs of the same feed-forward loop in the brains of people who died
while addicted to cocaine.
“The increased production of these proteins that we found in
the animals exposed to drugs was exactly paralleled in a population of human
cocaine addicts,” he said. “That makes us believe that the further experiments
and manipulations we did in the animals are directly relevant to humans.”
Robison said the growing understanding of addiction at the
molecular level could help pave the way for new treatments for addicts.
“This sort of molecular pathway could be interrupted using
genetic medicine, which is what we did with the mice,” he said. “Many
researchers think that is the future of medicine.”