Smoker’s Paradise: Research Zeros in on Brain’s Reward Pathway

Posted: March 8, 2010 at 1:00 am, Last Updated: March 5, 2010 at 3:48 pm

By Colleen Kearney Rich

Nadine Kabbani. Creative Services photo

The cigarette is perfectly designed to promote nicotine addiction, as are packs of cigarettes, says Mason molecular neuroscientist Nadine Kabbani.

“Tobacco companies have cracked the code to addiction very well,” Kabbani says. “In fact, they have managed to get the right amount of nicotine in a pack that will keep most people addicted.”

According to Kabbani, an expert in nicotine addiction and a researcher at Mason’s Krasnow Institute for Advanced Study, the average smoker will have a cigarette about every hour and a half.

The timing is based on the amount of nicotine in a cigarette and how that amount engages the nicotinic receptors in the brain.

All things addictive, whether a narcotic or a cigarette, have something in common, Kabbani says.

“What researchers are discovering is that these things happen to have targets within a specific brain pathway called the reward pathway. It is thought that anything that can perturb this pathway has addictive properties.”

Dopamine is a key neurotransmitter in the reward pathway. It is also linked to the pleasure system of the brain and is responsible for providing feelings of enjoyment that motivate a person to perform certain activities. In a way, addiction is “pleasure gone awry.”

Kabbani first became interested in the brain and the study of the mind as an undergraduate at Mason with a double major in psychology and biology.

After completing her Mason degrees, Kabbani was awarded a predoctoral fellowship at the Laboratory of Molecular Biology at the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. The fellowship played a pivotal role in her career.

“Work in that lab focused on early brain development, including stem cell research,” Kabbani says. “My project involved examining neural stem cell differentiation under various experimental cell culture conditions. I was incredibly excited by this type of research.”

Kabbani went on to pursue a doctorate in pharmacology at Pennsylvania State University. Before coming to Mason, she spent three years as a Phillip Morris Fellow at the Pasteur Institute in Paris, where she had the opportunity to work alongside Jean-Pierre Changeux, the scientist who first isolated the nicotinic receptor.

Kabbani also says that Paris is a good city in which to study nicotine addiction. “Everybody smokes,” she says. “It is a part of the French persona.”

Kabbani’s research focuses on the nicotinic receptors in the brain and takes place at the proteomic level, the level that deals with proteins within brain cells.

“Much of medicine right now is working on the protein level. For example, when you take an antihistamine drug for allergies, you are blocking a protein called the histamine receptor.”

There is still much to be learned about addiction. For example, why do some people become addicted to nicotine while others do not? And if it is somehow tied to pleasure, why are some pleasurable things addictive while others are not?

The answers lie in the brain’s chemistry.

The reward pathway, also called the mesolimbic pathway, touches many regions within the brain.

“Important neurotransmitters in these regions include dopamine and acetylcholine. Dopamine is currently the star because it is thought to be the main neurotransmitter in this pathway,” she says.

“An interesting thing about the nicotinic receptors that I work on is that not only do they bind nicotine directly, but they can also regulate dopamine levels in the brain.”

When people smoke, it affects their nicotinic receptors, which in turn regulate the release of dopamine in the brain. In the short term, this creates a new chemical brain environment, according to Kabbani.

As nicotine levels drop, a process called withdrawal begins, and the smoker is compelled to return to that chemical environment by having another cigarette or chewing a piece of nicotine gum.

Just as there are still things to be learned about addiction, the field of proteomics remains uncharted territory in the world of research, and there is a great deal of room for discovery.

“We know less than 20 percent of all the protein products of the human genome, so one obvious path for molecular biologists is to discover new proteins,” Kabbani says.

Long-range implications for her work include the possibility of discovering novel targets for future drug development.

“People say nicotine relaxes them and helps them focus, so this opens a path for thinking about nicotinic receptors as putative targets for cognitive enhancement drugs.”

This article appeared in a slightly different form in Mason Research 2010.

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