Reining in nicotine use: Midbrain habenula region plays key role in nicotine dependence

May 12, 2011

A person's vulnerability to nicotine addiction appears to have a genetic basis, at least in part. A region in the midbrain called the habenula (from Latin: small reins) plays a key role in this process, as Dr. Inés Ibañez-Tallon and her team from the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now shown. They also shed light on the mechanism that underlies addiction to nicotine.

According to the World Health Organization WHO in Geneva, it is estimated that tobacco use kills more than five million people each year worldwide. Many of them die of . "Two years ago, studies indicated that genetic variations in a specific gene cluster are risk factors for dependence and lung cancer," Dr. Ibañez-Tallon pointed out. She and her team, together with researchers from the Pasteur Institute in Paris, France and the Russian Academy of Sciences in Moscow, have now elucidated the mechanism underlying this dependence.

They investigated a specific receptor for the neurotransmitter acetylcholine, which is activated by nicotine in smokers and is encoded by this specific gene cluster, consisting of three subunits, that is three genes. "Although this gene cluster is present in the DNA of every cell, the receptor is only expressed in a few restricted areas of the brain. One of them is the habenula in the midbrain," Dr. Ibañez-Tallon explained.

The MDC researchers investigated this receptor and its subunits in egg cells of the African clawed frog (Xenopus laevis) and in transgenic mice. One of the three genes of the cluster is alpha5. "An important percentage of heavy smokers carry a single mutation in this gene. They are more prone to become addicted to nicotine and to develop lung cancer than individuals without this mutation," Dr. Ibañez-Tallon said.

Strong Aversion to Nicotine

A second gene in the encoding this receptor is beta4. The MDC researchers demonstrated that transgenic mice expressing high levels of the beta4 gene have increased sensitivity to nicotine. These mice have a strong aversion to drinking water containing nicotine.

However, when the researchers expressed the mutated variant of the alpha5 gene via a lentivirus in the habenular brain region of these mice, after only two weeks the mice showed a preference for nicotine. Dr. Ibañez-Tallon and her colleagues conclude that only a balanced activity of these two genes can rein in nicotine use.

More information: Neuron, May,12, 2011, Vol. 70, Issue 3, pp: 522-535; DOI 10.1016/j.neuron.2011.04.013

Related Stories

Recommended for you

Neuro chip records brain cell activity

October 26, 2016

Brain functions are controlled by millions of brain cells. However, in order to understand how the brain controls functions, such as simple reflexes or learning and memory, we must be able to record the activity of large ...

Can a brain-computer interface convert your thoughts to text?

October 25, 2016

Ever wonder what it would be like if a device could decode your thoughts into actual speech or written words? While this might enhance the capabilities of already existing speech interfaces with devices, it could be a potential ...

The current state of psychobiotics

October 25, 2016

Now that we know that gut bacteria can speak to the brain—in ways that affect our mood, our appetite, and even our circadian rhythms—the next challenge for scientists is to control this communication. The science of psychobiotics, ...

After blindness, the adult brain can learn to see again

October 25, 2016

More than 40 million people worldwide are blind, and many of them reach this condition after many years of slow and progressive retinal degeneration. The development of sophisticated prostheses or new light-responsive elements, ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.