Times have changed, and so has public perception of tobacco use. Every year, the percentage of U.S. adults who smoke cigarettes continues to decline, and more adults have quit successfully than ever before. For teens, smoking rates have also been diminishing steadily since 1997. Today's smokers benefit from a larger number of treatment methods, ranging from education and counseling to nicotine replacement therapy in the form of patches, gum and lozenges. Many ex-smokers have also benefited from Zyban - an anti-depressant shown to alleviate nicotine withdrawal symptoms - since it became available by prescription in 1998.
Yet, many smokers still find themselves unable to stop smoking completely, with each quit attempt eventually resulting in relapse. However, Dr. Ceylon Isgor believes that the "one size fits all" approach to current smoking cessation techniques doesn't address the specific, individual ways in which certain smokers become addicted to nicotine. "Individual differences in nicotine addiction play a major role in smoking cessation," Dr. Isgor explains, "and my research has found that when a person begins smoking plays a decisive role in how nicotine affects individual brain chemistry and level of addiction."
A 2005 New Investigator grant recipient at Florida Atlantic University, Dr. Isgor has found that smokers who began in their teens often have the most difficult time quitting completely. For many years, the importance of adolescence as a developmental phase was often overlooked, and "previous research focused on early childhood and adulthood, and adolescence was considered developmentally stagnant," she explains. "But we now know that major neurological development takes place during the teen years." At a time when neuronal connectivity is occurring at a rapid pace, "many addictive behaviors also tend to emerge," meaning that for teens who take up smoking, the physiological effects of nicotine - and the resulting addiction - may be even more pronounced.
Drawing upon recent advances in neuroscience, Dr. Isgor is investigating the personality trait of risk-taking, and the ways it may predetermine drug seeking and avoiding behavior. Individuals demonstrating a high-risk tolerance will voluntarily seek out novel sensory experiences, which may be partly determined by neurological factors. Previous drug addiction research has found that those who seek greater sensory stimulation also tend to develop a heightened neurological sensitivity to certain drugs, making them especially vulnerable to becoming addicted.
To better understand how an individual's risk-taking profile influenced subsequent addiction to nicotine, Dr. Isgor classified three groups of adolescent rats into "low, intermediate and high risk-taking profiles by the extent they moved around and explored their environment, with rats in the high-risk tolerance category demonstrating the greatest degree of motor activity." The rats were placed in behavioral sensitation boxes and given self-administered doses of nicotine. "High responders were given repeated doses of nicotine, and then put through repeated periods of withdrawal. Next, we challenged them with lower doses of nicotine, and again noticed increased motor activity, indicating craving." Put differently, rats in the high-risk tolerance category were willing to work harder to get another dose of nicotine.
"The goal of my work is to develop a trait-specific treatment targeting the specific neurotransmitters affected by nicotine." For many smokers, nicotine replacement and Zyban, while effective in offsetting many of the initial effects of withdrawal and craving, doesn't address the underlying neurological cues triggering addiction. "The relapse rate for Zyban is around 80 percent, but if we can introduce a drug that prevents the effects of nicotine altogether, relapse would be zero." Dr. Isgor has developed a class of drugs called CB1 receptor antagonists that block nicotine's effect on the brain by shutting down the receptors responsible for addition. "CB1 antagonists are unique because they can adapt to changing neurological conditions in the brain, providing consistent protection from addiction".
Dr. Isgor says progress on her CB1 research wouldn't be possible without the support of the James & Esther King Biomedical Research Program. "Thanks to this grant, my work has attracted the attention of leading neurobiologists, who are now turning their attention to individual differences in nicotine addiction," she said. She credits the creativity and foresight of the James & Esther King Program for their willingness to contribute to one of the most innovative avenues in current neuroscience research. "At a time when competition for resources is at an all-time high, I'm able to contribute to a body of work that has the potential to completely eliminate smoking."
