Response to reward measured in nicotine withdrawal

In a new study published in JAMA Psychiatry, scientists claim to have identified and measured the responses to rewards during nicotine withdrawal across humans and rats.

woman snapping a cigarette
Cigarette smoking is a leading cause of preventable death worldwide.

About 20% of the US population smoke cigarettes, although more than half of this group try to quit each year. However, less than 10% of smokers attempting to quit are able to remain smoke-free, with most relapses occurring within 48 hours of cessation.

Cigarette smoking is a leading cause of preventable death worldwide.

Researchers want to understand more about the process of withdrawal and why people have difficulty quitting smoking. A greater understanding of the mechanisms at work should lead to more effective treatments to help smokers quit for good.

The researchers behind the new study say that “response to reward” is the brain’s ability to derive pleasure “from natural things such as food, money and sex.” Depression is associated with a reduced ability to respond to reward.

The scientists, from Florida Atlantic University in Boca Raton, University of California San Diego, Harvard Medical School in Boston, MA, and Washington University School of Medicine in St. Louis, MO, used what they call a “translational behavioral approach” to take different behavioral measurements from the rats and humans.

Analyzing the behaviors, the researchers found that nicotine withdrawal had a similar effect on reducing reward responsiveness in both human smokers and nicotine-treated rats. This reduced responsiveness was particularly strong in smokers with a history of depression.

The researchers explain that their study breaks new ground as it is the first study of its kind to replicate experimental results across species. They say this cross-species analysis allows for greater generalizability and provides a more reliable way to identify neurobiological mechanisms.

Research could lead to therapies targeting reward dysfunction

Lead author Michele Pergadia, PhD, associate professor of clinical biomedical science in the Charles E. Schmidt College of Medicine at Florida Atlantic University, says:

“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.”

Pergadia says that future studies will look more closely at how depression vulnerability relates to reward sensitivity, as well as mapping the full course of withdrawal-related reward deficits in an effort to develop new smoking cessation aids.

“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,” she adds.

In 2013, JAMA Psychiatry also published a study investigating whether prenatal exposure to maternal cigarette smoking had an effect on response to reward.

The researchers compared a group of 177 adolescents who had been exposed to maternal cigarette smoking prenatally with 177 peers matched by sex and maternal educational level who had not been exposed.

Analyzing activity in the ventral striatum area of the brain using functional magnetic resonance imaging, the researchers in that study reported a weaker response during reward anticipation in the prenatally exposed teens compared with the non-exposed teens.

However, the study reports no differences between the responsively of the ventral striatum in the exposed and non-exposed teens upon receipt of the reward. The authors wrote:

“The weaker responsivity of the ventral striatum to regard anticipation in prenatally exposed adolescents may represent a risk factor for substance use and development of addiction later in life. This result highlights the need for education and preventive measures to reduce smoking during pregnancy.”

Written by David McNamee

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