Young woman snorting cocaine

Cocaine use causes ‘feed-forward’ loop

MICHIGAN STATE (US) — Scientists have found a molecular chain reaction in the brain triggered by cocaine, and say that interrupting this process could provide treatment for addiction.

Researchers say cocaine alters the nucleus accumbens, the brain’s pleasure center 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,” says A. J. Robison, assistant professor in the department of physiology and the neuroscience program at Michigan State University.

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.

In their research published in the Journal of Neuroscience, 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,” says Robison.

Robison says the study also 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 says. “That makes us believe that the further experiments and manipulations we did in the animals are directly relevant to humans.”

Robison says 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 says. “Many researchers think that is the future of medicine.”

Source: Michigan State University

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