Adolescent binge drinking produces tolerance to alcohol

October 14, 2003

The 2000 National Household Study on Drug Abuse reports that close to 20 percent of young people between 12 and 17 years of age had consumed alcohol in the preceding month; more than 10 percent reported a "binge" style of drinking, defined as consumption of five or more drinks on one occasion. In the October issue of Alcoholism: Clinical & Experimental Research, researchers use adolescent rodents to demonstrate that a binge pattern of alcohol consumption called chronic intermittent ethanol (CIE) exposure can significantly hamper normal growth and alter brain function.

"We found that CIE exposure during adolescence produces tolerance, defined as a decrease in the response to a drug due to previous exposure with the drug, in many wide-ranging, biological functions," said Douglas B. Matthews, associate professor of psychology at The University of Memphis and corresponding author for the study. "For example, CIE exposure significantly hampered normal growth as measured by weight gain, and altered liver function as measured by alcohol elimination rates. In addition, CIE exposure appears to alter brain function, as measured by hypnotic and cognitive tolerance. While it is currently unknown if CIE exposure is more serious in adolescence than adulthood, the current research does demonstrate that the tolerance produced by CIE during adolescence can last into adulthood."

Researchers used 135 male Sprague-Dawley rats for four experiments. On postnatal day 30 (the rodent equivalent of adolescence), pretreatment consisted of injecting all of the rats with 5.0 g/kg alcohol or saline every 48 hours for 20 days. For experiment I, 24 rats (12 pretreated with alcohol, 12 with saline) were given free access to food and water. For experiment II, loss of righting reflex (the animal's inability to right itself and return to all fours) was observed in 24 rats (12 pretreated with alcohol, 12 with saline) after each injection. For experiment III, blood alcohol levels were observed and elimination rates calculated for 17 rats (9 pretreated with alcohol, 8 with saline) after the first and fifth pretreatments, then all animals were tested with 5.0 g/kg at completion of pretreatment and elimination rates were recalculated. For experiment IV, 70 rats (36 pretreated with alcohol, 34 with saline) were trained on a maze task on nontreatment days and, after completing pretreatment and training, were tested after an alcohol challenge (1.0, 1.5 or 2.0 g/kg) or saline. Tests for experiments II, III and IV were repeated in the same animals following 12 alcohol-free days.

"The key finding of this set of studies is that CIE exposure during adolescence produces profound tolerance that in some cases can last into adulthood," said Matthews. "These findings suggest adolescence as a unique developmental period where exposure to high alcohol levels can produce changes in biological functions that might have long-lasting implications."

Despite numerous studies in recent years, "still very little is known about the long-term effects of alcohol consumption on adolescents," said Linda Patia Spear, Distinguished Professor in the department of psychology and the Center for Developmental Psychobiology at Binghamton University. "In humans, a substantial number of studies have shown that the earlier individuals start using alcohol, the more likely they are to have alcohol-related problems in adulthood, although it is not known whether this early exposure is causal or is just a marker for problematic alcohol involvement. In studies using laboratory animals, there are likewise some initial hints that adolescent alcohol exposure influences later sensitivity to alcohol, although the available data to date are mixed, and studies often do not include adult-exposure comparison groups so it is not clear as to whether these effects are more or less pronounced than would be seen after equivalent exposure in adulthood."

Despite the lack of consistent data, Matthews said two factors - the developmental nature of adolescence, and recent national reports of growing use and abuse of alcohol by adolescents - underscore the need for additional information. He and his colleagues will next investigate the effects of CIE exposure during adolescence on genetic expression in the brain, the activity of single neurons in the brain, and the biochemical mechanisms producing these effects.

"It is critical to determine whether the effects observed following these very high dose exposures are more pronounced or less pronounced than after comparable exposure in adulthood," suggested Spear. "It would also be important to determine whether similar findings would also be evident at somewhat lower ethanol exposure levels that do not induce marked growth stunting and might be more analogous to ethanol exposure levels of human adolescents. Furthermore, it would also be interesting to try to dissect the circumstances under which CIE exposure during adolescence results in later ethanol tolerance, as in the present study, versus a later sensitized response as has been occasionally reported by others."
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 included Janelle M. Silvers, Sayaka Tokunaga, and Guy Mittleman of The University of Memphis. The study was funded by the Alcoholic Beverage Medical Research Foundation and The University of Memphis.

Alcoholism: Clinical & Experimental Research

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