Alcoholism And Excessive Food Intake May Share Chemical Pathways In The Brain

"Galanin's well-known effects of increasing food intake, especially the intake of fat-rich diets, was one of the early reasons we investigated it," said Michael J. Lewis, a senior fellow working with Dr. Bart Hoebel in his laboratory in the Department of Psychology at Princeton University and Sarah Leibowitz at Rockefeller University, and corresponding author for the study. "Alcohol is the only drug of abuse that can also qualify as a calorie-rich food, and it undoubtedly has important interactions with systems that control food intake and nutrition."

Lewis added that alcohol, galanin and food intake have another area of commonality: all are stimulants of the neurotransmitter dopamine, which has been linked by numerous studies to the rewarding effects and "high" produced by potent drugs of abuse such as nicotine, cocaine and heroin.

"While many brain neurochemicals have been examined for their role in modulating neurobiological responses to alcohol, the role of neuropeptide pathways, particularly those that have been shown to be involved with feeding and body weight regulation, have largely been ignored," added Todd E. Thiele, associate professor in the department of psychology at the University of North Carolina at Chapel Hill. "Recent research has implicated a number of peptides and proteins known to control food intake in alcohol consumption, including neuropeptide Y, cholecystokinin, the melanocortins, and leptin. This paper is one of the first demonstrations of an important role for galanin in modulating alcohol intake, and at the same time adds to the growing list of peptides that may have overlapping control of both alcohol and food ingestion."

For this research, male Sprague Dawley rats were surgically implanted with a cannula in a brain region next to the third ventricle, and given access to increasing concentrations of alcohol for a 12-hour light/12-hour dark day cycle until all had acquired a preference for seven-percent alcohol over water in a two-bottle choice.

"Rats are nocturnal animals and sleep during the light and feed and engage in other normal behaviors during the darkness," noted Lewis.

The rats were then given three microinjections – galanin alone, galanin in combination with a galanin receptor antagonist, and the galanin receptor antagonist alone – to determine effects on alcohol and water intake. Tests were conducted during both the light and dark periods of the day cycle. Food was freely available; however, as a control for galanin-induced calorie intake, both the alcohol and food were measured in a subset of rats during the dark period of the day cycle.

"The injection of galanin into the third ventricle increased alcohol intake, but not water," said Lewis. "This effect was found during both the light and dark cycles. However, the effect was more dramatic during the light cycle when rats are not normally eating or drinking. These effects were blocked by a galanin receptor antagonist. Furthermore, galanin did not increase food intake in those animals that had been chronically consuming alcohol."

"A key finding is that a galanin receptor antagonist by itself reduces alcohol drinking," observed Thiele. "This suggests a possible role for galanin receptor antagonists in the treatment of uncontrolled alcohol drinking, otherwise known as alcohol dependence or alcoholism."

These results, in conjunction with previous findings that alcohol intake increases galanin in the paraventricular nucleus, have led the authors to speculate that galanin may play a role in the development of alcohol dependence through what they call "a positive feedback mechanism."

"Current data show that galanin can increase alcohol intake," said Lewis. "Previous research from our labs has shown that consumption of alcohol can increase the levels of galanin in the hypothalamus, particularly a region called the paraventricular nucleus. In other words, galanin stimulates alcohol intake, which then can increase galanin in the brain, in what might become a vicious cycle."

"The concept of a 'positive feedback mechanism' is interesting," said Thiele. "Such a mechanism could help explain the uncontrolled alcohol drinking that is characteristic of an alcoholic. For example, human alcoholics often cannot stop drinking alcohol once they begin. However, more research is needed to determine if galanin plays a role in human, as opposed to rodent, alcohol drinking. Taken collectively, however, these are important findings because they introduce a new candidate neurochemical system that may be involved in modulating alcohol consumption. In fact, if alcoholism and obesity are controlled by overlapping chemical pathways in the brain, then drugs effective at treating obesity may be useful for treating alcoholism in some cases."

"In summary," said Lewis, "our data suggest that there may be a close link between the brain mechanisms that control the motivation to drink alcohol and those that control the intake of food. Perhaps there should be a renewed focus in alcohol research on understanding the interrelationship and overlap between the mechanisms that control food intake and nutrition with those involved with excessive alcohol intake and dependence. It is conceivable that galanin plays an important role in the excessive drinking of alcohol dependence. For example, the role of galanin may be altered in alcoholics such that instead of increasing food intake, it motivates drinking. It is clear, however, that alcohol dependence is complex, involving several brain systems. Our research suggests that galanin may be one of them."

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Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper, "Galanin microinjection in the third ventricle increases voluntary ethanol intake, " were: Deanne F. Johnson, Daniel Waldman, and Bartley G. Hoebel of the Department of Psychology at Princeton University; and Sarah F. Leibowitz of the Laboratory of Behavioral Neurobiology at The Rockefeller University, New York City. The study was funded by the National Institute on Alcohol Abuse and Alcoholism.