August 28, 2000

Even the first few puffs from a cigarette can have your brain begging for more, because nicotine alters the brain's reward areas, according to scientists at the University of Chicago Medical Center. By uncovering and understanding these cellular mechanisms of nicotine's effects, they believe new drugs can be designed to block the powerful craving that nicotine creates.

The brain's reward areas serve to reinforce healthy behavior, such as eating when you're hungry. Dopamine, a neurotransmitter associated with pleasant feelings, is released by these reward areas to encourage the body to repeat these behaviors. However, drugs like nicotine that stimulate the brain can bypass these normal reinforcement pathways, providing the same rewards for harmful behaviors as for beneficial ones.

The initial exposure to nicotine can be remembered by the brain, which will amplify the effects of the drug and boost the desire to have another cigarette, according to the study published in the August 2000 issue of Neuron. Nicotine appears to cause addiction by strengthening the excitatory connections between the neurons that make dopamine, which are found in the ventral tegmental area (VTA) of the brain reward center. This strengthening excites the neurons, which then release dopamine into the reward center.

"This appears to be the crucial first step in the process of addiction," said neurobiologist Daniel McGehee. "Now that we know how this happens, we can begin to search for better ways to intervene."

In studies with rats, McGehee and Dr. Huibert Mansvelder demonstrated how nicotine takes control of the brain's reward pathways. Nicotine alters the connections between neurons using a process that is similar to the cellular mechanisms that create memory. "In this way, the brain erroneously learns that the intake of nicotine was good and remembers sensations it caused," said Mansvelder.

This reinforcing effect is the primary reason people get hooked on smoking and can't quit, despite knowing the harmful effects the behavior. Nicotine dependence has been estimated to cause 70 times more deaths in the United States than all other types of drug dependence combined. The scientists report that nearly 25 million Americans alive today will die prematurely from smoking-related illnesses. "Nicotine addiction makes millions of people suck carcinogens into their lungs over and over again, day after day," said McGehee. "If this knowledge leads to new ways of helping people quit successfully, it will be an important step for public health worldwide.

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