Researcher team explores alcohol, nicotine link

August 1, 2002

The strong connection between smoking and drinking has long been noted by the public at large and documented by social scientists, public health experts and clinical researchers. Scientists in the department of pharmacology and neuroscience at UNT Health Science Center have been looking at the issue from the perspective of pharmacogenetics, or the role of genetics in modulating the actions of a drug.

The husband-wife research team of Christopher M. de Fiebre, PhD, assistant professor, and NancyEllen de Fiebre, senior research associate, both of pharmacology and neuroscience, has uncovered new evidence that supports the theory that common genetic factors influence sensitivity to both alcohol and nicotine. Their findings were recently published in the June issue of Alcoholism: Clinical & Experimental Research. The National Institute on Alcohol Abuse and Alcoholism funded the study.

â??Numerous studies in the last several decades have confirmed that drinking and smoking are positively correlated,â? Dr. de Fiebre said. â??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.â?

Their work began with the knowledge that whether an individual develops alcoholism or becomes dependent on tobacco is mediated by both genetic and environmental factors. â??We then hypothesized that common genetic factors were involved in modulating sensitivity to both alcohol and nicotine and this, in turn, influenced the development of the co-abuse of these two agents,â? he said.

In a laboratory model, they found that being highly sensitive to alcohol corresponded with a high level of sensitivity to nicotine on one of several measures of nicotine sensitivity examined. Similarly, being insensitive to alcohol corresponded with being insensitive to nicotine.

â??The key finding of this study is that there appears to be a commonality in the genes that modulate the actions of both nicotine and alcohol,â? Dr. de Fiebre said. â??Some, but not all, of the genes that modulate sensitivity to alcohol are probably the same as some, but not all, of the genes that modulate sensitivity to nicotine.

â??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,â? he said.

The specific genes that might be responsible for modulating the actions of both alcohol and nicotine remain largely unknown, however, the de Fiebres hypothesize that the genes that encode receptors for nicotine may be involved, and they are examining this possibility.

â??Perhaps surprisingly, many genes influence sensitivity to even simple responses to alcohol. It is very doubtful that thereâ??s one single gene that acts as a predictor of addiction,â? Dr. de Fiebre said. â??Our research is part of an effort to try to unlock the secrets to addiction. Ideally, we would like to identify all the genetic factors that affect a bodyâ??s reaction to drugs of abuse, primarily those effects that are driving the addiction process.â?

Future studies that include both alcohol and nicotine may yield answers to questions that have remained unresolved when the two drugs have been studied singly.

â??If we can gain a better understanding of how co-abused drugs work together and decipher those genetic factors that modulate co-addiction, perhaps we can design more rational therapies to treat the problem,â? he said.

Although much of the de Fiebresâ?? work focuses on the effects of alcohol and nicotine, their research is not limited to the effects of those drugs.

As a â??nicotinic pharmacologist,â? Dr. de Fiebre studies nicotinic receptors, the sites in the brain at which nicotine acts, and tries to ascertain how these receptors contribute not only to addiction, but to other pathologies, such as Alzheimer’s disease and other neurodegenerative disorders.

â??The studies published in Alcoholism are a small part of the puzzle that we are trying to solve â?? the role of nicotinic receptors in pathology,â? Dr. de Fiebre said. â??By gaining a better understanding of how common genes modulate the actions of both alcohol and nicotine, we can start asking which genes are involved in the development of alcohol and nicotine co-addiction and then use this information to develop rational therapies for this form of polydrug addiction.â?

The de Fiebres are also interested in what role nicotinic receptors or nicotinic systems play in normal brain function. â??Clearly we donâ??t have nicotinic receptors so that we can abuse tobacco products. These receptors exist because we have within us a specific chemical called acetylcholine that normally activates these receptors to do something essential for normal brain function,â? he said.

Research has suggested that one normal function of nicotinic receptors is to assist in keeping nerve cells healthy and alive. Because of this, the de Fiebre research team is also examining the role of nicotinic receptors in Alzheimer’s disease or alcohol-induced brain cell death and whether nicotine or drugs that mimic some of the actions of nicotine might be useful in treating these disorders.

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