Heavy Drinking and Alcoholism are Linked to Different Genes

 Genes that contribute to high alcohol consumption are not the same as those that predispose to alcoholism, new research suggests.

Investigators from the University of Colorado, Denver, found that in rats and in humans, genetic make-up may predispose individuals to drink more but may not increase the genetic risk for alcoholism. This study pinpoints genetic pathways and genes associated with levels of alcohol consumption but not with alcohol dependence.

“The main impact of our findings with regard to human alcohol consumption and alcoholism is that our studies dissociate the brain mechanisms that control levels of alcohol consumption from those mechanisms that produce psychiatrically defined alcoholism,” principal investigator Boris Tabakoff, PhD.

“The definition and characteristics of alcoholism primarily involve a state in which the individual cannot reduce his/her drinking, cannot abstain from drinking, and in which the person’s life becomes centered on obtaining and drinking alcohol. Many lay individuals, and even those in the medical profession, equate a high amount of alcohol drinking with alcoholism. Our studies indicate that the genetic predisposition to drinking high levels of alcohol in a controlled manner is different than those genetic predisposing factors that produce loss of control/drinking. Thus, high levels of alcohol intake do not necessarily equate to alcohol dependence,” he added.

Disorders Not the Same

However, Dr. Tabakoff also noted that research by his team does indicate that high levels of alcohol intake are necessary for the neural changes that lead to dependence. “Thus, alcohol intake can be considered an ‘environmental predisposing factor’ to alcohol dependence development. In a nutshell, levels of alcohol intake are not biologically the same as alcohol dependence,” he said.

The research team used rats to identify the genetic pathways affecting alcohol drinking behavior. They found that the rats’ drinking behavior was linked to the pleasure and reward pathways in the brain and was also linked to some of the same genetic systems that control satiety and appetite for food.

Next, the researchers directly compared genes involved in these alcohol-associated pathways in rats with the human versions of these genes in 2 male study groups from Montreal, Canada, and Sydney, Australia, to identify common genetic factors linked to alcohol use across species. This analysis showed that that genes identified as contributors to drinking behavior in the tested populations were not the same as the genes found to predispose to alcohol dependence.

Eating and Drinking Mechanisms Linked

“The implications for alcoholism research are fairly significant. We can say that the study of alcohol drinking per se in animals, including humans, may not produce appropriate insights into the determinants of alcoholism. Additionally, if one is trying to develop medications to treat alcoholism using animal models that simply measure drinking in nondependent animals, the studies may not produce results that would indicate efficacy of a drug in a situation where an individual is alcohol dependent,” said Dr. Tabakoff.

The researchers were surprised at the similarity of the alcohol-related pathways to those that normally control ingestive behaviors in general. “Since alcohol has caloric value, part of the rewarding property of alcohol in a nondependent individual may have to do with systems that have been developed to monitor and maintain the body’s energy needs,” he said.

This raises the intriguing question of whether medications that were developed for control of appetite for food might be useful for controlling an individual’s drinking levels.

“Our studies do strongly indicate that we should be looking at alcohol consumption and alcohol dependence differently, both from the perspective of biological drives and mechanisms and, as well, for developing treatment strategies — be they medications or psychotherapy,” Dr. Tabakoff said.

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