Dietz Finds Potential New Target to Treat Cocaine Addiction

The researchers’ molecular studies show that a reduction in expression of the protein, called Rac1, drives structural changes in the brain that increase its sensitivity to cocaine’s rewarding effects.

Among the most important changes is the large increase in the number of physical protrusions, or spines, that grow out from the neurons in the brain’s reward center. The spines’ presence demonstrates the spike in the reward effect that an individual receives from cocaine exposure.

“This suggests that Rac1 may control how exposure to drugs of abuse, like cocaine, may rewire the brain in a way that makes an individual more susceptible to the addicted state,” says David Dietz, PhD, assistant professor of pharmacology and toxicology, who conducted the research while at Mount Sinai School of Medicine.

By changing the level of expression of Rac1 in mice, Dietz and his colleagues were able to control whether or not they became addicted.

The researchers conducted the experiment with a novel tool that allowed for light activation to control Rac1 expression—the first time that a light-activated protein has been used to modulate brain plasticity.

“We can now understand how proteins function in a very temporal pattern, so we could look at how regulating genes at a specific time point could affect behavior, such as drug addiction, or a disease state,” says Dietz.

Dietz is continuing his research on the relationship between behavior and brain plasticity at UB. He and his team are looking at how plasticity might determine how much of a drug an animal takes and how persistently the animal tries to get the drug.

The study was published in Nature Neuroscience in an article titled “Rac1 is essential in cocaine-induced structural plasticity of nucleus accumbens neurons.”

The National Institute on Drug Abuse and the National Institute of Mental Health funded the research.