Chronic cocaine use triggers changes in brain's neuron structure

The research, led by UB's Dietz, suggests a potential new target for development of a treatment for cocaine addiction. Credit: Douglas Levere, UB Communications

Chronic exposure to cocaine reduces the expression of a protein known to regulate brain plasticity, according to new, in vivo research on the molecular basis of cocaine addiction. That reduction drives structural changes in the brain, which produce greater sensitivity to the rewarding effects of cocaine.

The finding suggests a potential new target for development of a treatment for . It was published last month in by researchers at the University at Buffalo and Mount Sinai School of Medicine.

"We found that chronic cocaine exposure in mice led to a decrease in this protein's signaling," says David Dietz, PhD, assistant professor of pharmacology and toxicology in the School of Medicine and Biomedical Sciences, who did the work while at Mt. Sinai. "The reduction of the expression of the protein, called Rac1, then set in motion a cascade of events involved in structural plasticity of the brain -- the shape and growth of in the brain. Among the most important of these events is the large increase in the number of physical or spines that grow out from the neurons in the of the brain.

"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 Dietz.

The presence of the spines demonstrates the spike in the reward effect that the individual obtains from exposure to cocaine. By changing the level of expression of Rac1, Dietz and his colleagues were able to control whether or not the mice became addicted, by preventing enhancement of the brain's reward center due to .

To do the experiment, Dietz and his colleagues used a novel tool, which 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.

In his UB lab, Dietz is continuing his research on the relationship between behavior and , looking, for example, at how plasticity might determine how much of a drug an animal takes and how persistent the animal is in trying to get the drug.

Related Stories

Researchers discover why cocaine is so addictive

Oct 18, 2010

Mount Sinai researchers have discovered how cocaine corrupts the brain and becomes addictive. These findings -- the first to connect activation of specific neurons to alterations in cocaine reward -- were published in Science on Oct ...

Tuning cocaine addiction

Jul 19, 2010

small bits of genetic material that influence gene expression - reduces the urge for a cocaine fix in mice, according to a paper published online on July 19 in the Journal of Experimental Medicine.

Recommended for you

Myelin vital for learning new practical skills

Oct 16, 2014

New evidence of myelin's essential role in learning and retaining new practical skills, such as playing a musical instrument, has been uncovered by UCL research. Myelin is a fatty substance that insulates ...

Reminiscing can help, not hinder, some mind-bending tasks

Oct 16, 2014

To solve a mental puzzle, the brain's executive control network for externally focused, goal-oriented thinking must activate, while the network for internally directed thinking like daydreaming must be turned down to avoid ...

Bio-X scientists develop decoy drug to aid ailing brain

Oct 16, 2014

A team of Stanford Bio-X scientists has restored the ability of adult mice to form new connections in the brain. If the finding works in people, it has the potential to help adults recover from stroke and ...

User comments