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Nicotine primes brain for cocaine use: Molecular basis of gateway sequence of drug use
Date:11/2/2011

Cigarettes and alcohol serve as gateway drugs, which people use before progressing to the use of marijuana and then to cocaine and other illicit substances; this progression is called the "gateway sequence" of drug use. An article in Science Translational Medicine by Amir Levine, MD, Denise Kandel, PhD; Eric Kandel, MD; and colleagues at Columbia University Medical Center provides the first molecular explanation for the gateway sequence. They show that nicotine causes specific changes in the brain that make it more vulnerable to cocaine addiction -- a discovery made by using a novel mouse model.

Alternate orders of exposure to nicotine and cocaine were examined. The authors found that pretreatment with nicotine greatly alters the response to cocaine in terms of addiction-related behavior and synaptic plasticity (changes in synaptic strength) in the striatum, a brain region critical for addiction-related rewards. On a molecular level, nicotine also primes the response to cocaine by inhibiting the activity of an enzyme―histone deacetylase―in the striatum. This inhibition enhances cocaine's ability to activate a gene called FosB gene, which promotes addiction.

The relationship between nicotine and cocaine was found to be unidirectional: nicotine dramatically enhances the response to cocaine, but there is no effect of cocaine on the response to nicotine. Nicotine's ability to inhibit histone deacetylase thus provides a molecular mechanism for the gateway sequence of drug use.

Nicotine enhances the effects of cocaine only when it is administered for several days prior to cocaine treatment and is given concurrently with cocaine. These findings stimulated a new analysis of human epidemiological data, which shows that the majority of cocaine users start using cocaine only after they have begun to smoke and while they are still active smokers. People who begin using cocaine after they've started smoking have an increased risk of cocain
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Contact: Stephanie Berger
sb2247@columbia.edu
212-305-4372
Columbia University's Mailman School of Public Health
Source:Eurekalert

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