Scientists Find How Nicotine Affects Brain

Researchers at Columbia-Presbyterian Medical Center 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 how nicotine may be addictive as well as how it alters mood and improves alertness and cognition. The finding may also open the door for the development of an anti-addiction treatment in the future.

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 Lorna Role, associate professor in the department of anatomy and cell biology in the Center for Neurobiology and Behavior at Columbia-Presbyterian Medical Center. "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 nicotine acts on presynaptic receptors to boost transmission.

Another problem is that 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 typical concentrations of nicotine 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 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 Mark Heath, assistant professor of anesthesiology at Columbia's College of Physicians and Surgeons, 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," he said.

Other authors on the study are Shari Gelber and Piroska Devay, both with Columbia-Presbyterian Medical Center.

The study was funded by awards to Role from the National Institutes of Health, the McKnight Foundation, and the Council for Tobacco Research.

Columbia University Record -- September 29, 1995 -- Vol. 21, No. 4