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One thing leads to another


Addiction to alcohol or nicotine often precedes the use of cocaine and other illegal substances. A recent study points to the possible neural basis of this phenomenon (Sci. Trans. Med. 3, 107ra109).

Amir Levine et al. pretreated mice with nicotine and found that it increased addiction-related behaviors such as conditioned place preference in response to cocaine. This effect was unidirectional; exposing the mice first to cocaine did not affect responses to nicotine.

Mechanistically, the authors found that nicotine enhanced the ability of cocaine to inhibit histone deacetylase, promoting histone acetylation in the nucleus accumbens, a key component of the brain reward system. This priming magnified the effect of cocaine on synaptic plasticity in the accumbens. Indeed, pharmacologically or genetically manipulating histone acetylation correspondingly modified the effects of cocaine on plasticity.

Analyzing epidemiological data, Levine et al. showed that cocaine use often occurs in smokers. Moreover, people who initiate cocaine use after they become smokers are most likely to develop cocaine dependence. Decreasing smoking rates might therefore lead to a decrease in cocaine addiction.


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López, J. One thing leads to another. Nat Med 17, 1566 (2011).

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