Mar. 17, 2006 Vulnerability to both alcohol and nicotine abuse may be influenced by the same genetic factor, according to a recent study supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH).
In the study, two genetically distinct kinds of rat -- one an innately heavy-drinking strain bred to prefer alcohol ("P" rats), the other strain bred to not prefer alcohol ("NP" rats) -- learned to give themselves nicotine injections by pressing a lever. Researchers found that P rats took more than twice as much nicotine as NP rats. Their findings were reported recently in the Journal of Neuroscience.
"Our findings suggest that the genetic factor underlying the high alcohol consumption seen in P rats may also contribute to their affinity for nicotine," said lead author A.D. Lê, Ph.D., a NIAAA-supported researcher at Toronto's Centre for Addiction and Mental Health and University of Toronto.
Researchers have known for some time that people who smoke are more likely to drink alcohol than non-smokers. Similarly, smoking is three times more common in people with alcoholism than in the general population. Since previous studies have also determined that genetics plays an important role in both alcohol and nicotine addictions, researchers have hypothesized that the same gene or genes may influence the co-abuse of these substances.
Investigating this hypothesis in human studies is stymied by the possibility that alcohol use leads to nicotine use, and vice versa. However, in the current study, researchers showed that the P rats' affinity for nicotine could be demonstrated before the animals were ever exposed to alcohol.
P rats were also found to be more vulnerable to nicotine relapse than NP rats. Researchers withheld nicotine from the rats until their lever pressing occurred infrequently. Then, both P and NP rats were given a single nicotine injection. P rats, but not NP rats, resumed pressing the lever previously associated with nicotine infusions.
The researchers also showed that the P rats' apparent genetic vulnerability to alcohol and nicotine does not appear to extend to other drugs of abuse. When P and NP rats learned to press a lever to receive cocaine, each group took about the same amount of that drug. The authors note that the lack of a difference in cocaine self-administration indicates that the difference between P and NP rats in nicotine self-administration is not due to a general "reward deficit" in NP rats.
"Selectively-bred P rats have been a reliable and useful animal model for studying diverse behavioral and physiological characteristics of alcohol abuse," notes NIAAA Director and study co-author Ting-Kai Li, M.D. "These findings suggest that they may be as useful for studying nicotine addiction. And by expanding our knowledge of the genetic underpinnings of alcohol and nicotine co-morbidity these findings will inform our efforts to address those important public health issues."
Other co-authors included Drs. Z. Li, D. Funk, and M. Shram, of the Centre for Addiction and Mental Health, and Dr. Yavin Shaham of the Behavioral Neuroscience Branch, National Institute on Drug Abuse, part of the National Institutes of Health (NIH).
Reference: A. D. Lê, Z. Li, D. Funk, M. Shram, T. K. Li, and Y. Shaham Increased Vulnerability to Nicotine Self-Administration and Relapse in Alcohol-Naive Offspring of Rats Selectively Bred for High Alcohol Intake
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