Alcohol's Effects on the Adolescent Brain What Can Be Learned From Animal Models

Because of legal and ethical constraints on alcohol research in human adolescents, many studies of alcohol's effects on the developing brain have been conducted in animal models, primarily rats and mice. The adolescent brain may be uniquely sensitive to alcohol's effects because major changes in brain structure and function occur during this developmental period. For example, adolescent animals are more sensitive than adults to the effects on memory and learning that result from alcohol's actions on the hippocampus. Conversely, adolescent animals appear to be less sensitive than adults to alcohol-related motor impairment, alcohol-induced sedation, and the development of seizures during withdrawal. Alcohol exposure during adolescence can have long-lasting effects and may interfere with normal brain functioning during adulthood. KEY WORDS: adolescent; binge drinking; animal study; animal model; physiological AODE (alcohol and other drug effects); biological development; brain; brain function; cognition; learning; memory; motor coordination; AODR (alcohol and other drug related) seizure; hippocampus; neurotransmitter receptors ********** Adolescence and young adulthood are developmental stages of transition during which humans, as well as members of many other species, mature physically and behaviorally into their adult state. Adolescents and young adults need to acquire the physical and behavioral skills that will allow them to live independently of their parents, sustain themselves, and reproduce. This period is marked by more frequent and sophisticated social interactions with peers, exploration of new situations and behaviors, and an increased willingness to take risks. In humans, this often involves the initiation of alcohol and other drug use. At the same time, the brain undergoes considerable structural and functional changes, at least in part in response to the individual's many new experiences. Connections among nerve cells (neurons) in the brain can change based on which neurons or groups of neurons are regularly stimulated, a characteristic known as plasticity. This natural process serves to eliminate unnecessary or unused nerve cell connections, (1) allowing the survival of only those neurons that make meaningful contacts with other neurons. This winnowing of neurons is influenced by, among other factors, the adolescent's interactions with and experiences in the outside world. Adolescence is such a critical phase in brain development that the actions of alcohol and other drugs on the brain can be assumed to have a particularly profound impact during this developmental period. Indeed, research has shown that compared with the adult brain, the adolescent brain is particularly sensitive to some effects of alcohol, yet more resistant to other effects. Much of this research, especially investigations of specific effects of acute alcohol administration, has been conducted in animals because studies involving administration of alcohol to human adolescents are subject to very stringent regulations, and certain studies of alcohol's effects on the adolescent brain can be conducted only using animal models. This article reviews some of the differences in alcohol's effects on the adolescent and adult brain that were identified using these animal models. The accompanying article by Tapert and colleagues (pp. 205-212) summarizes information that has been obtained in studies of human adolescents and young adults. MAJOR CHANGES IN BRAIN STRUCTURE AND FUNCTION DURING ADOLESCENCE Adolescence in humans is broadly defined as the second decade of life, although some researchers consider ages up to 25 years as "late adolescence. " The corresponding period in laboratory animals that are frequently used as study subjects is just as loosely defined. In rats it typically spans postnatal days 30-50 (i.e., PD30-PD50). In both humans and animal models, adolescence is a period when the brain undergoes extensive remodeling. …