Source: The Associated Press Pubdate: Wed, 6 May 1998 RATS' NICOTINE WITHDRAWAL STUDIED NEW YORK (AP) -- Rats going through nicotine withdrawal showed a brain reaction similar to what's seen in amphetamine and cocaine withdrawal, which might help explain nicotine craving in people who've quit cold turkey. The finding might also help scientists develop better ways of treating the symptoms of nicotine withdrawal, such as depression, anxiety, irritability and craving, all of which interfere with attempts to kick the habit, said Dr. Alan I. Leshner, director of the National Institute on Drug Abuse. NIDA helped pay for the study, which appears in Thursday's issue of the journal Nature. The study focused on brain circuitry that produces pleasure from activities like eating and sex. It found that during nicotine withdrawal, this ``reward'' system became harder to turn on, just as previous studies had found for withdrawal from other drugs. In people who've just stopped smoking, that could cause depressive symptoms like losing interest in activities that used to be rewarding, said Athina Markou, who reports the work with colleagues at the Scripps Research Institute in La Jolla, Calif. She believes such emotional aspects of nicotine withdrawal are important contributors to craving. So if scientists can find drugs that make the brain reward system easier to activate, the medications might be able to ease nicotine craving, she said. The rats activated their brain reward circuitry by turning a wheel, which made electrical current run into electrodes in their brains. Scientists recorded how much current the rats needed, which revealed how sensitive the circuitry was. Then rats were given a constant supply of nicotine through tiny pumps, producing blood levels about equal to smoking a pack-and-a-half a day. After seven days, the pumps were removed to produce withdrawal. The amount of current the rats needed to feel reward shot up, peaking some six to eight hours after their nicotine supply was cut off. The effect persisted an average of four days. - --- Checked-by: "R. Lake"