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CENTURY
Yale University
School of Medicine
SAC-203
Connecticut
Mental Health Center
34 Park Street
New Haven, CT 06519

Phone:
203-974-7591

Fax:
203-974-7606

E-mail:
infocentury@yale.edu

CENTURY/TTURC Press Release

New Haven, Conn. - New Haven, CT – A new study by Yale researchers has shown that prior nicotine exposure in mice can increase their motivation to work for food, weeks after their last exposure to nicotine.

The study, to be published in an upcoming issue of 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," said Dr. Darlene Brunzell, Ph.D., first author of the study. Animals exposed to nicotine showed increased motivation to poke their nose for food almost five weeks after their last exposure, said Dr. Marina Picciotto, Ph.D., an associate professor in the Departments of Psychiatry, Pharmacology and Neurobiology at Yale, and a principal investigator with the Transdisciplinary Tobacco Use Research Center. "Weight gain associated with smoking cessation may reflect nicotine-associated enhancement of the reinforcing value of food,” said Dr. Brunzell. “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 push once and get a pellet, then three times, then five and so on, said Dr. 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 said.

"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," said Dr. Stephanie O'Malley, the TTURC principal investigator. “More research is needed to determine how exactly 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,” said Dr. Brunzell.  “These studies show that Beta 2 nicotinic receptors are necessary for nicotine's ability to increase the control that cues have over behavior."

Dr. Brunzell said 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 said.

Dr. Picciotto said the study suggests that novel treatments being developed by some drug companies to target certain nicotinic acetylcholine receptors (the a 4/ b 2*nAChRs) likely will be effective in combating the reinforcing effects of nicotine and its ability to increase responding to reward-related cues. She added, however, that these drugs might not have effects on weight gain or craving for food in abstinent smokers.

Dr. O'Malley said that the research has significance when it comes to developing solutions for smokers who gain weight after they quit smoking. She noted 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 said, the research might help discourage people from starting to smoke to regulate their weight.

The citation for the study is Brunzell, D.H., Chang, J. R., Schneider, B., Olausson, P., Taylor, J.R., Picciotto, M.R. (2005) B2-Subunit-containing nicotinic acetylcholine receptors are involved in nicotine-induced increases in conditioned reinforcement but not progressive ratio responding for food in C57BL/6 mice. Psychopharmacology.

The full article will be available online for two months from the date of publication at

http://www.springerlink.com/openurl.asp?genre=article&id=doi:10.1007/s00213-005-0099-z

To find out more about Psychopharmacology and to sign up for its alert service, that would provide email notification of new content in the journal, please go to

http://www.springeronline.com/213

CENTURY and TTURC were created to help people quit smoking. The focus of the research at Yale is smokers who have the greatest need for help, those who cannot quit or have trouble doing so. One of the primary goals of the initiative is to encourage and support research that integrates theories and methods from different disciplines.

TTURC was created with a grant from the National Institute on Drug Abuse (NIDA), the National Cancer Institute (NCI) and grants from The Robert Wood Johnson Foundation. Yale TTURC is one of seven centers around the country conducting a wide variety of transdisciplinary tobacco-related research.

NIDA¹s mission is to bring the power of science to bear on drug abuse and addiction. This charge has two critical components: The first is the strategic support and conduct of research across a broad range of disciplines. The second is to ensure the rapid and effective dissemination and use of the results of that research to significantly improve drug abuse and addiction prevention, treatment and policy.

The National Cancer Institute (NCI) is part of the National Institutes of Health (NIH), one of eight agencies that make up the Public Health Service in the Department of Health and Human Services. The NCI, established under the National Cancer Act of 1937, is the Federal Government¹s principal agency for cancer research and training. The National Cancer Act of 1971 broadened the scope and responsibilities of the NCI and created the National Cancer Program.

The Robert Wood Johnson Foundation, based in Princeton, N.J., is the nation¹s largest philanthropy devoted exclusively to health issues. Its mission is to improve the health and health care of all Americans. One of the Foundation¹s grant-making priorities is to reduce the personal, social and economic harm caused by abuse of substances such as tobacco, alcohol and illicit drugs.