Addiction researchers are both familiar with and intrigued by the strong connection between smoking and drinking. Recent human studies have suggested that one or more genes may play a critical role in increasing vulnerability to alcohol and tobacco addiction. A study in the June issue of Alcoholism: Clinical & Experimental Research uncovers new evidence which supports the theory that common genetic factors influence sensitivity to both alcohol and nicotine, the alkaloid responsible for many of the effects of tobacco, including addiction.
"Numerous studies in the last several decades have confirmed that drinking and smoking are positively correlated," said Christopher M. de Fiebre, assistant professor of pharmacology and neuroscience at the University of North Texas Health Science Center at Fort Worth, and corresponding author for the study. "Nowhere is this association seen as clearly as in alcoholic populations. While the percentage of smokers in the general American population has decreased over the last several decades, the rate of smoking among alcoholics has remained at approximately 90 percent, a rate well above that seen in nonalcoholic populations. We knew that whether an individual develops alcoholism or becomes dependent on tobacco is mediated by both genetic and environmental factors. We hypothesized that common genetic factors were involved in modulating sensitivity to alcohol and nicotine and this, in turn, influenced the development of the co-abuse of these two agents."
Male and female rats selectively bred for high (HAS), low (LAS), and control (CAS) sensitivity to alcohol were tested for nicotine sensitivity using several different measures. The HAS rodents were found to be more sensitive to one measure in particular – nicotine-induced locomotor activity depression – than the LAS rodents. Researchers also measured plasma and brain levels of nicotine and its primary metabolite, cotinine, as well as the binding of three nicotinic ligands in eight brain regions. Since no differences in plasma or brain nicotine levels were seen between the HAS and LAS rodents, the authors speculate that the HAS/LAS differences arise because of differences in the sensitivity of the central nervous system (CNS) to nicotine.
"The authors’ speculation is actually a very logical conclusion," said Allan C. Collins, professor of pharmacology and behavioral genetics at the University of Colorado. "Many years of research done by many laboratories have demonstrated that mice, rats, and humans may differ in behavioral reactions to a drug for two primary reasons: differences in drug pharmacokinetics, or differences in brain or CNS sensitivity." The pharmacokinetics of a drug refers to the way it moves through the body, including its absorption into the circulation, its distribution to different parts of the body, its metabolism, and eventual elimination. "The authors measured the pharmacokinetic parameters via plasma and brain levels and found no difference," continued Collins. "This leaves brain or CNS differences in sensitivity as the most likely explanation."
"The key finding of this study is that there appears to be a commonality in the genes which modulate the actions of both nicotine and alcohol," said de Fiebre. "Some, but not all, of the genes which modulate sensitivity to alcohol are probably the same as some, but not all, of the genes which modulate sensitivity to nicotine. Although we do not currently know which genes are responsible for modulating the actions of these two drugs … we hypothesize that the overlap in genes controlling sensitivity to these two drugs may in part explain why smokers drink and drinkers smoke."
"Which genes may be responsible for modulating the actions of alcohol and nicotine? The answer to this question remains largely unknown," said Collins. "However, these findings add to the data base which argues that common genes influence some of the behavioral actions of two of the most frequently abused drugs. It may be that studies that include both alcohol and nicotine may yield answers to questions that have remained unresolved for many years when the two drugs have been studied singly. Interestingly, Joe Medium and Sally Average have known for years that alcoholics are smokers. Yet this ‘common knowledge’ has been, by and large, ignored by the scientific community. This paper will not change life as Joe and Sally know it, but it may help them to understand that there are biological or genetically determined reasons that contribute to individual differences in vulnerability to both alcohol and tobacco abuse."