may actually increase it, study suggests
A new study by Yale researchers shows that prior nicotine exposure in mice can increase their motivation to work for food, weeks after their last exposure to nicotine.
The study, published in Psychopharmacology, sheds new light on the role played by certain nicotinic acetylcholine receptors when it comes to the reinforcing aspects of nicotine. It also provides insight into one of the most vexing issues relating to smoking cessation, one that discourages many people from attempting to quit smoking, the prospect of weight gain.
The findings run counter to the popular belief that nicotine exposure curbs appetite. "Although acute nicotine can act as an appetite suppressant, these data are the first to suggest that repeated exposure to nicotine has the opposite effect, that nicotine increases motivation for food for weeks following exposure to the drug," says Darlene Brunzell, associate research scientist in the Department of Psychiatry and first author of the study.
Animals exposed to nicotine showed increased motivation to poke a lever with their noses for food almost five weeks after their last exposure, notes Marina Picciotto, associate professor in the Departments of Psychiatry, Pharmacology and Neurobiology, and a principal investigator with the Transdisciplinary Tobacco Use Research Center (TTURC).
According to Brunzell, "Weight gain associated with smoking cessation may reflect nicotine-associated enhancement of the reinforcing value of food. With a goal of long-term weight maintenance and good health, people would be best advised not to use nicotine as an appetite suppressant."
The study measured whether and how hard mice would work for food under certain conditions. The mice were motivated to work for food by being mildly food restricted. They also were trained to push a lever for food on a progressive ratio schedule, with the number of times they had to push for the next pellet steadily increasing. So, first they pushed once and got a pellet, then three times, then five and so on, explains Picciotto.
"After some amount of pushing, the animal will give up and we interpret that as the animal saying: 'This is not worth it!' The nicotine treated animals pushed many more times than the nicotine-naive animals for food," she says.
Stephanie O'Malley, professor of psychiatry and the TTURC principal investigator, says, "This research suggests that when young people take up smoking to regulate their weight, this may be counterproductive in addition to being harmful to their health. More research is needed to determine exactly how that works, but this does show that there could be a connection between acute exposure to nicotine and subsequent weight gain in some individuals."
In addition, the study identifies which nicotinic receptors are involved in nicotine's control over cues. "We knew previously that cues play a critical role in nicotine and tobacco consumption in animals and humans," says Brunzell. "These studies show that beta 2 nicotinic receptors are necessary for nicotine's ability to increase the control that cues have over behavior."
Brunzell says the role of the beta 2 receptors in nicotine's primary reinforcing effects, in combination with the receptors' ability to strengthen cues associated with smoking, might be the key to why people find quitting so difficult. Compounds that inhibit the beta 2 nicotinic receptors may help to decrease cue-dependent cigarette craving and relapse to smoking, she says.
Picciotto says the study suggests that novel treatments being developed by some drug companies to target certain nicotinic acetylcholine receptors (the _4/_2*nAChRs) likely will be effective in combating the reinforcing effects of nicotine and its ability to increase response to reward-related cues. She adds, however, that these drugs might not have effects on weight gain or craving for food in abstinent smokers.
O'Malley says that the research has significance when it comes to developing solutions for smokers who gain weight after they quit smoking. She notes that weight concerns keep many people, particularly women, from attempting to quit. Any information about the mechanism for weight gain could help the researchers at Yale and elsewhere figure out how to address that concern. In the meantime, she says, the research might help discourage people from starting to smoke to regulate their weight.
-- By Pem McNerney
T H I S
W E E K ' SS T O R I E S
Yale community extends helping hand to the victims of Hurricane Katrina
Yale leaders contribute $70,000 to match employee and student donations
Student donates prize money to aid victims of hurricane
Panel examined why Katrina was 'a perfect storm' of failure
Brenzel named undergraduate admissions dean
Studies explore function and formation of feathers
Chinese president's visit postponed
ENDOWED PROFESSORSHIPS
Richard L. Cohn: Battell Professor of the Theory of Music
Lawrence Manley: William R. Kenan Jr. Professor of English
Robert S. Nelson: Robert Lehman Professor of the History of Art
Susan C. Stokes: John S. Saden Professor of Political ScienceNBA star to discuss his humanitarian efforts in the Congo
Director Sofia Coppola to give Chubb Lecture
Labor-management training aims to foster cooperation
Project explores how cultural outlook impacts opinions
MEDICAL SCHOOL NEWS
NIH gives $3.6 million for research to alleviate anxiety . . .
Common pesticide linked to reduced fertility in women
Most implanted embryos are not viable, says study
Study: Hormone therapy for menopause leads to fewer wrinkles
Nicotine, long thought to curb appetite, may actually increase it . . .
Research shows brain distinguishes between odors inhaled . . .
Schizophrenics with diabetes still receive antipsychotic drugs . . .
Medical school offering clinical trial of new treatment . . .'Days of Caring'
Event celebrates 400-year anniversary of 'Don Quixote'
Symposium to examine history of U.S. reach into the Pacific
Scientist Pan invited to participate in NAE symposium
Electrical engineer T.P. Ma is honored for solid-state research
In weekly series, World Fellows will debate global topics
University will celebrate Constitution Day on Sept. 20
Multimedia artist presents photo exhibit and video installation at ISM
'A Taste of Bulgaria' to aid flood victims in another corner of the world
Urban infra-power and urban charisma to be explored in conference
Search committee named for School of Art dean
Biophysical chemist Julian Sturtevant . . .
Memorial service scheduled for . . . Robert Abelson
Alumni magazine now reaches every Yale graduate in the U.S.
Campus Notes
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