Veil Lifted on Nicotine’s Powerful Grip on the Brain : Health: Scientists at last discover how chemical works. They say the findings may aid in treatment of addiction.
After decades of searching, researchers have finally discovered the way nicotine exerts its potent physiological effects on the brain cells of smokers. The finding should help explain not only why the substance is addictive, but also how it alters mood, improves alertness and increases the ability to concentrate.
The discovery, reported today in the journal Science, may open the door for the development of an anti-addiction treatment for smokers, as well as new approaches to the treatment of Alzheimer’s disease and certain other mental disorders.
“This is an extremely exciting story,” said neuroscientist Edythe D. London of the National Institute on Drug Abuse. “This is particularly important” not only for what it tells us about the actions of nicotine, but also because it illuminates the normal role of a well-known class of chemicals in the brain, called nicotinic cholinergic receptors, which play a role in many crucial brain functions.
Neurobiologist Lorna W. Role and her colleagues at the Columbia University College of Physicians and Surgeons found that other scientists have, in effect, been looking in the wrong place in the brain for clues to nicotine’s mechanisms.
Most researchers have assumed that nicotine directly mimics the activity of a conventional neurotransmitter--binding to the receiving end of a brain cell and stimulating an electrical signal.
But in its study of chicken brain cells, Role’s group unexpectedly found that nicotine works indirectly, binding at the transmitting end of the brain cell, where the cell releases chemicals that signal the next cell in line.
By binding at the transmitter, nicotine stimulates the release of greater than usual quantities of a chemical called glutamate, one of the key neurotransmitters involved in the pleasure response in the brain.
The nicotine appears to strengthen communication between the cells, like turning up the volume on a radio, Role said. This may explain how it makes the user more alert, for example.
“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, and does so at such extremely low concentrations” said Role’s colleague, neurobiologist Daniel S. McGehee of Columbia.
By binding at the transmitter, McGehee said, nicotine’s effects are multiplied so that it can exert an effect much greater than would be expected from its actual concentration.
Furthermore, these effects are exerted primarily in the limbic system of the brain, which “encourages the individual to reproduce, to eat and to perform all the basic drives” by making them pleasurable, Role said. It now seems clear, she noted, that the nicotinic cholinergic receptors mediate these responses, and that nicotine enhances their effects.
“These pathways in the brain encode information that essentially says, ‘That was good! Do it again!’ ” she said. “Nicotine interacts in a very potent way in these areas. That’s why people are willing to inhale a couple of hundred class A carcinogens in order to get some of it.”
The knowledge of how nicotine works is crucial to scientists searching for ways to block its activity and thereby help smokers quit. Knowing what it does should enable them to develop new strategies to block its activity, such as specially designed drugs that will bind at the same location and prevent it from working, the scientists say.
“The whole issue in nicotine and addiction research has been to try to find the molecular systems in which it acts,” said Columbia neuroscientist Eric Kandel, who was not involved in the research. “Lorna’s finding . . . is a very promising insight into how it exerts its effects in the brain.”
The discovery may have implications far beyond its contribution to the debate over the merits of smoking. Defects in the nicotinic cholinergic receptors that Role’s group studied have also been shown to play a role in the development of Alzheimer’s disease, and they may have a function in Parkinson’s disease and schizophrenia as well. Some studies suggest that administration of nicotine to Alzheimer’s victims can, at least temporarily, restore some lost brain functions.
“Now we have a much better idea why some of the aspects of Alzheimer’s disease can be ameliorated by exposure to nicotine,” Role said. That insight could lead to new treatments, she added.
Role, McGehee and their associates studied chicken brain cells suspended in test tubes. They applied extremely small quantities of nicotine to the cells and monitored its effect. Eventually, they were able to show that it bound to the transmitter end of the cell, enhancing the release of neurotransmitters.
The system they used may prove valuable as a screening tool for developing new anti-smoking drugs, Kandel said. Currently, researchers have to use addicted animals to study the effects of prospective drugs, an expensive and time-consuming process. The chicken cell system, he added, provides a simple and direct measure of a chemical’s anti-smoking potential, and could greatly speed up the search for new drugs.
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Nicotine in the Brain
Although signals are carried through brain cells electrically, they are carried across the gaps (synapses) between cells by chemicals called neurotransmitters. A new discovery indicates that researchers were looking at the wrong place in the brain to discover how nicotine exerts its pleasurable effects. They found that it boosts production of neurotransmitters.
Researchers had though nicotine binds to receiving side (Dendrite of neutron B)
New study finds nicotine binds to transmitting side (Terminal of neuron A)
Source: Los Angeles Times
