Dramatic changes in the brain's pleasure circuits during withdrawal from chronic nicotine use rival the magnitude and duration of similar changes observed during withdrawal from other 
abused drugs such as cocaine, opiates,amphetamines, and alcohol, according to a new study funded by the NationalInstitute on Drug Abuse (NIDA), National Institutes of Health. Scientists atThe Scripps Research Institute found significant decreases in the sensitivityof the brains of laboratory rats to pleasurable stimulation after nicotineadministration was abruptly stopped.
These changes lasted several days, andmay correspond to the anxiety and depression experienced by humans for several days after quitting smoking "cold turkey." "Understanding these decreases in the brain's sensitivity to pleasurable stimulation that occur during nicotine abstinence helps explain why it is so hard for people to stop smoking. This understanding may
also help in the development of better treatments to address the withdrawal symptoms -
depression, anxiety, irritability, and craving - that interfere with people's attempts to quit 
smoking," said Dr. Alan I. Leshner, director of NIDA. "The similarity to other drugs of abuse emphasizes that there are common characteristics to withdrawal from all addictive substances, one of which is a decrease in sensitivity to pleasure."

A research team led by Dr. Athina Markou of The Scripps Research Institute inLa Jolla, California measured the effects of nicotine withdrawal and abstinence on the brain's sensitivity to pleasurable electrical stimulation.  Researchers allowed rats to self-administer a baseline 
intensity of pleasurable electrical pulses and measured "pleasure" (or reward) associatedwith stimulation of the area of the lateral hypothalamus, part of the brain'sreward circuitry. Reward sensitivity measures were taken both during and afteradministration of nicotine.

For one week, the rats were given a steady dose of nicotine that produced blood levels equivalent to those of an individual smoking one and a half packsof cigarettes a day. While the nicotine was being administered, the rats'sensitivity to brain reward remained stable, as indicated by no significantchange in the self-administration of the electrical pulse. When the rats weretaken off nicotine, however, intensities of electrical current had to beincreased by more than 40 percent before the rats again found them to be pleasurable. Brain reward sensitivity was affected for at least 4 days and some rats did not return to baseline for over 2 weeks.

"These results are comparable to the altered brain reward sensitivity found also during 
withdrawal from many other addictive drugs," said Dr. Markou. "The results of this research indicate that we have a good animal model to study the neurobiology of nicotine abstinence and thus assist in the development of behavioral and pharmacological treatments for nicotine addiction." This research was funded in part by Novartis Pharma AG of Basel, Switzerland. The study, "Dramatic decreases in brain reward function during nicotinewithdrawal," will be 
published in the May 7 issue of NATURE.

The use of nicotine products is a major preventable cause of death in the United States. About 
62 million Americans age 12 and over are current cigarette smokers, making nicotine one of 
the most heavily used addictive drugs. The scientific facts about nicotine addiction, based on 
the latest research, will be the focus of Addicted to Nicotine: A National Research Forum to be held July 27-28, 1998. The conference, sponsored by NIDA, the Robert Wood Johnson 
Foundation, the National Cancer Institute, and the Centers for Disease Control and Prevention's Office on Smoking and Health will highlight the sources of nicotine addiction, prevention of tobacco product use, and state-of-the-art treatment strategies. The conference will be held at 
the Natcher Auditorium on the NIH Campus in Bethesda, MD. For more information, contact the NIDA Press Office.