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How nicotine makes the brain vulnerable to cocaine

Kathleen Blanchard's picture
Nicotine as a gateway to cocaine abuse

Research suggests nicotine is a gateway to cocaine abuse.

Using a new mouse model, scientists from Columbia University's Mailman School of Public Health found out how nicotine changes an area of the brain to increase vulnerability to cocaine addiction and perhaps other drugs.

The researchers of the study say the finding is the first to explain how nicotine primes the brain by changing its plasticity. The result of smoking cigarettes and using other nicotine products activates the reward center of the brain that is linked closely to cocaine addiction.

For the study, the investigators exposed mice to nicotine in their drinking water for at least seven days. When they exposed the rodents to cocaine, reaction to cocaine in the brain become more pronounced.

The scientists found nicotine increased the strength of synaptic responses in the brain which is related to addictive behaviors.

The researchers explain nicotine also inhibits the activity of an enzyme -- histone deacetylase -- in the striatum. The result is activation of a gene called FosB, which promotes addiction.

"These studies raise interesting questions that can now be explored further in animal models," said study author Denise Kandel, a professor of Sociomedical Sciences at the Mailman School of Public Health.

Do alcohol and marijuana -- the two other gateway drugs -- prime the brain by the same mechanism as nicotine? Is there a single mechanism for all gateway sequences, or does each sequence utilize a distinct mechanism?"

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The enhanced response to cocaine was only noted when nicotine was administered within days and at the same time of cocaine exposure. The study failed to find a reverse association. Cocaine did not prime the brain for nicotine addiction.

When the researchers concurrently compared the mouse finding to human epidemiological data, they found most cocaine users began after they had started to smoke.

They also discovered nicotine use increases the likelihood of becoming addicted to cocaine.

In the concurrent analysis, the authors found that 81% of youths reported actively smoking tobacco when they started using cocaine, compared to just 18.8% of non-smokers.

Past studies have shown nicotine and cocaine activate the same receptors in the brain.

Daniel McGehee, PhD, neuroscientist and associate professor in the Department of Anesthesia & Critical Care at the University of Chicago Medical Center, said, "We know that a single exposure to physiologically relevant concentrations of nicotine can lead to changes in the synaptic drive in the circuitry that lasts for several days. That idea is very important in how addiction forms in humans and animals.”

The authors of the current study say their finding suggests public health programs are needed to curb the use of all nicotine products, especially among youth.

"If our findings in mice apply to humans, a decrease in smoking rates in young people would be expected to lead to a decrease in cocaine addiction," the authors wrote.

The study, published in Science Translational Medicine, is the first to show specifically how nicotine acts to change synaptic response and plasticity in the brain making tobacco products a gateway for cocaine and other drug abuse.

Image credit: morguefile