Associate Professor Athina Markou, Ph.D., who is in the Scripps Research Molecular and Integrative Neurosciences Department at Scripps Research’s La Jolla Campus, and Paul Kenny, Ph.D., a former Research Associate in her laboratory, report in an upcoming issue of the journal Neuropsychopharmacology that nicotine has an unusual psychological property that may drive dependence.
Nicotine induces a long-lasting activation of the brain's reward systems that is not seen after excessive consumption of other drugs of abuse, such as cocaine or heroin. This slight elevation in mood is there regardless of how much nicotine is consumed, and it persists long after the nicotine is gone from the body.
“It’s almost a memory of nicotine in the brain,” says Kenny, who is now a staff scientist at Scripps Florida. “The reward system becomes hyperactive, even when the nicotine isn’t there.”
This persistence of reward activity, Kenny adds, appears unique to nicotine among drugs of abuse and is probably crucial in maintaining the nicotine habit. Knowing this may have relevance to prevention of nicotine addiction and smoking cessation programs.
Nicotine is one of thousands of chemical components of cigarette smoke, and it is the main ingredient in tobacco that leads to addiction, which fuels cigarette smoking, a major health problem in the United States. The latest report of the U.S. Surgeon General on the health effects of smoking calls it the leading preventable cause of death in American society. And according to the U.S. Centers for Disease Control and Prevention (CDC), one in five deaths in the United States is related to smoking, and more than 400,000 Americans die each year from it—through cancer, cardiovascular disease, and respiratory diseases.
In the last few years, Markou and her colleagues at Scripps Research and at Novartis Pharma AG have been funded by a multi-year, $3.45 million grant from the National Institute of Mental Health (NIMH) and the National Institute on Drug Abuse (NIDA) to design new ways to treat depression and nicotine addiction. One of the goals of this grant is to look at the connection between cigarette smoking and depression, which could shed light on what makes nicotine so addictive, and how the same sorts of compounds used to treat depression might be used to treat nicotine addiction.
Their interest in the connection between cigarette smoking and depression is what led Markou and Kenny to study the effect of nicotine on the brain’s natural reward system. Although nicotine does not induce intoxication, Markou and Kenny expected the neurobiology of nicotine addiction to be similar to other addictive substances such as cocaine and heroin, in which these chemicals affects neurocircuitry in the reward centers of the brain and induce a measurable elevation in mood directly related to the presence of these drugs. This pleasurable action likely contributes to establishing the drug habit. Then, hours later when cocaine or heroin is no longer present, there is a diminished sensitivity to rewarding stimuli – the so-called ‘crash’ associated with drug withdrawal.
In their study, Markou and Kenny looked at the effect of nicotine self-administration on brain reward systems in laboratory rodents. They allowed the rodents to have extended access to nicotine self-administration, and they directly measured the changes in neuronal activity in the brain.