NICOTINE WITHDRAWAL REDUCES RESPONSE TO REWARDS ACROSS SPECIES
Cigarette smoking is a
leading cause of preventable death worldwide and is associated with
approximately 440,000 deaths in the United States each year, according to the
U.S. Centers for Disease Control and Prevention, but nearly 20 percent of the
U.S. population continues to smoke cigarettes. While more than half of U.S.
smokers try to quit every year, less than 10 percent are able to remain
smoke-free, and relapse commonly occurs within 48 hours of smoking cessation.
Learning about withdrawal and difficulty of quitting can lead to more effective
treatments to help smokers quit.
In a first of its kind
study on nicotine addiction, scientists measured a behavior that can be
similarly quantified across species like humans and rats, the responses to
rewards during nicotine withdrawal. Findings from this study were published
online on Sept. 10, 2014 in JAMA Psychiatry.
Response to reward is
the brain's ability to derive and recognize pleasure from natural things such
as food, money and sex. The reduced ability to respond to rewards is a
behavioral process associated with depression in humans. In prior studies of
nicotine withdrawal, investigators used very different behavioral measurements
across humans and rats, limiting our understanding of this important brain
reward system.
Using a translational
behavioral approach, Michele Pergadia, Ph.D., associate professor of clinical
biomedical science in the Charles E. Schmidt College of Medicine at Florida
Atlantic University, who completed the human study while at Washington
University School of Medicine, Andre Der-Avakian, Ph.D., who completed the rat
study at the University of California San Diego (UCSD), and colleagues,
including senior collaborators Athina Markou, Ph.D. at UCSD and Diego
Pizzagalli, Ph.D. at Harvard Medical School, found that nicotine withdrawal
similarly reduced reward responsiveness in human smokers -- particularly those
with a history of depression -- as well as in nicotine-treated rats.
Pergadia, one of the
lead authors, notes that replication of experimental results across species is
a major step forward, because it allows for greater generalizability and a more
reliable means for identifying behavioral and neurobiological mechanisms that
explain the complicated behavior of nicotine withdrawal in humans addicted to
tobacco.
"The fact that
the effect was similar across species using this translational task not only
provides us with a ready framework to proceed with additional research to
better understand the mechanisms underlying withdrawal of nicotine, and
potentially new treatment development, but it also makes us feel more confident
that we are actually studying the same behavior in humans and rats as the
studies move forward," said Pergadia.
Pergadia and
colleagues plan to pursue future studies that will include a systematic study
of depression vulnerability as it relates to reward sensitivity, the course of
withdrawal-related reward deficits, including effects on relapse to smoking,
and identification of processes in the brain that lead to these behaviors.
Pergadia emphasizes
that the ultimate goal of this line of research is to improve treatments that manage
nicotine withdrawal-related symptoms and thereby increase success during
efforts to quit.
"Many smokers are
struggling to quit, and there is a real need to develop new strategies to aid
them in this process. Therapies targeting this reward dysfunction during
withdrawal may prove to be useful," said Pergadia.
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