How does Nicotine Switch the Brain onto Cocaine?

A new study indicates that nicotine primes the brain for cocaine - by altering the structure of a gene linked to learning, memory and addiction.
05 December 2011


Teenagers who smoke cigarettes and drink alcohol are opening a 'gateway' for subsequent addiction to cannabis or cocaine, new research suggests.

This relationship was first suggested in the 1970s but there has been speculation over whether this effect was due to environmental factors, like peer pressure and drugs access, or if physical changes in the brain were to blame.

But a study published in the journal Science Translational Medicine provides a possible brain based explanation for this phenomenon.  

Dr. Amir Levine and his colleagues at Columbia University New York and New York State Psychiatric Institute discovered, using experimental mice, that nicotine effectively primes the brain for cocaine addiction.

By looking in the striatum - an area of the brain involved in reward, pleasure and addiction, they found that nicotine treatment for just seven days triggered certain nerve cells to add molecules called acetyl groups to an addiction linked gene called FosB.  This leads to a process called "hyperacetylation" of the protein that DNA is wound around, histone.  This then changed the physical structure of the gene, opening it up and leading to a much stronger expression of the FosB gene when cocaine was subsequently administered.  

According to lead author of the study, Dr Amir Levine, "Nicotine basically opens up chromatin [genetic material] and that is how it primes the brain to the effects of cocaine."

Next, looking in humans, the researchers found that people addicted to cocaine are more likely to have been active smokers at the time of first time of taking the drug than to not smoke.   Dr Amir Levine comments:

"[We saw that] the ones who smoked first in their history, and then used cocaine, there was a 20% chance that they would become addicted to cocaine, whereas the ones still smoking, still using cocaine, but they started cocaine first, before smoking ... their chances of getting addicted to cocaine was much smaller, about 6%." says Levine

The scientists point out that although the number of people they analysed was small, the data does provide some evidence that the molecular priming mechanism seen in mice may also be present in humans, contributing to a human nicotine gateway effect.

These results give rise to further questions - Do other drugs, such as alcohol, elicit similar effects?  Does nicotine prime the brain to switch on addiction to other drugs such as heroin and crystal meth?  Should nicotine even be legal in the first place?  Do these results explain the biological mechanism by which nicotine exerts its cognitive enhancing effect? And could these findings actually help us to discover a new therapy to help beat, or even prevent, all types of addiction?


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