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P&S Journal

P&S Journal: Winter 1996, Vol.16, No.1
Research Reports
Research Finds Key Nicotine Switch in the Brain

Researchers have discovered a molecular mechanism in the brain that may explain nicotine's potent physiological effects. The mechanism is triggered by nicotine in concentrations normally found in smokers.

The finding, reported in the Sept. 22 issue of Science, could help explain nicotine's addictive nature and how it alters mood and improves alertness and cognition. The finding also may open the door to development of anti-addiction treatment.

Nicotine acts on a novel nicotinic receptor complex, identified by the Columbia group, that is strategically located at the sites of communication between neurons in the brain. At very low concentrations, nicotine activates the receptor and causes the neuron to release more neurotransmitter. The result is a much stronger signal. The researchers believe that nicotine's ability to strengthen signals between neurons may account for the complex behavioral effects of nicotine, such as increased alertness and improved short-term memory.

"Nicotine apparently can increase the strength of communication between neurons in the brain by increasing the release of glutamate-the key central nervous system excitatory transmitter," says principal investigator Dr. Lorna Role, associate professor of anatomy and cell biology in the Center for Neurobiology and Behavior. "These presynaptic receptors are ideal targets for nicotine because of their location, high sensitivity to nicotine, and efficacy in enhancing transmitter release."

Part of the problem in understanding the complex effects of nicotine in the brain has been that researchers primarily have looked for nicotine's effects on transmission via postsynaptic receptors. This study indicates that nicotine acts on presynaptic receptors to boost transmission. Many studies of nicotine's actions have involved exposure to high doses of nicotine-much larger than the average smoker takes in. The newly identified nicotinic receptor complex is sensitive to concentrations of nicotine typically found in smokers.

"What has been so mysterious about nicotine is that it has a broad spectrum of action that produces cognitive and behavioral effects for which there is no explanation," says first author Dr. Daniel McGehee. "By learning how these receptors operate in a normal brain, we can understand what role they might play in addictive effects of nicotine."

Coauthor Dr. Mark Heath, assistant professor of anesthesiology, says the study strengthens the view that nicotine is a powerful substance in controlling brain function. "Cigarette smoking is one of the biggest health problems in the world. This study may help explain the role of nicotine in making cigarettes such a difficult habit to break."

copyright ©, Columbia-Presbyterian Medical Center

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