Behavioral and Physiological Consequences of Early Drinking

by National Institute of Health

(Page 3 of 3)

Although increased tolerance to alcohol's sedative effects may enable greater intake in adolescents, repeated exposure to alcohol may produce increased sensitivity to alcohol's harmful effects. Studies in rats show that ethanol-induced inhibition of synaptic potentials mediated by N-methyl-D-aspartate (NMDA) and long-term potentiation (LTP) is greater in adolescents than in adults. Initially, the developmental sensitivity of NMDA currents to alcohol was observed in the hippocampus, but more recently this effect was found outside the hippocampus in pyramidal cells in the posterior cingulate cortex. Behaviorally, adolescent rats show greater impairment than adults in acquisition of a spatial memory task after acute ethanol exposure in support of greater LTP sensitivity to alcohol in adolescents. Behavioral and neurobiological mechanisms for the ontogenetic differences in alcohol tolerance and sensitivity are unclear, as is the relationship between differential sensitivity to ethanol and onset of alcohol abuse and alcoholism.

Binge alcohol exposure (i.e., chronic intermittent exposure to high alcohol doses) in rats during adolescence produces long-lasting changes in memory function and interferes with the normal development of sensitivity to alcohol-induced motor impairments. In addition, prolonged alcohol exposure during adolescence, but not adulthood, produces alterations in neurophysiological response to ethanol challenge, tolerance to the sedative effects of ethanol, enhanced expression of withdrawal-related behavior, and long-lasting neurophysiological changes in the cortex and hippocampus in rats. Further more, chronic ethanol treatment in rats may lead to increased NMDA-mediated neurotoxicity, which could be exacerbated by repeated withdrawals. Consistent with this hypothesis is the finding that severity of alcohol and drug withdrawal symptoms may be a powerful marker of neuropsychological impairments in detoxified older human adolescents and young adults. Moreover, one recent study found reduced hippocampal volumes in human adolescents with a history of alcohol abuse/dependence disorder and another preliminary investigation of alcohol-abusing teenagers observed subtle white-matter microstructure abnormalities in the corpus callosum, which may be a precursor of more severe damage produced by long-term chronic drinking. Juvenile rats exposed to heavy bingelike episodes of ethanol have greater damage than adults in frontal-anterior cortical regions, including the olfactory frontal cortex, anterior perirhinal, and piriform cortex. Thus, the immature brain may be more susceptible to binge ethanol-induced neurotoxicity, although the mechanisms are unknown.

Because teenagers are likely to engage in binge drinking, it is important to study the effects of chronic binge patterns of ethanol exposure on brain structure, neurochemistry, and cognitive functioning. Care must be taken in extrapolating from the described animal studies to the binge-drinking adolescent. Because binge drinking does not usually entail withdrawal, it is important to distinguish between damage caused by the alcohol itself and that caused by repeated withdrawals. In addition, primate models may be a better choice for studying the long-term consequences of alcohol exposure because of primates' prolonged adolescent period, which allows extensive manipulation of different types and lengths of exposure. These models, coupled with new neuroanatomical and neuroimaging techniques, offer a unique opportunity to study the brain changes associated with adolescent drinking and determine whether adolescent brains are able to recover more easily because of greater plasticity.

Early Exposure as a Predictor of Later Alcohol Abuse

Early exposure to alcohol - at or before age 14 - is strongly associated with later alcohol abuse and dependence. Two possible explanations for this effect are obvious. First, early alcohol use may simply be a marker for later alcohol abuse rather than a causative factor. A good deal of evidence indicates that at least one behavioral factor, behavioral undercontrol, is measurable very early in life and is a consistently robust predictor of earlier alcohol use as well as of elevated risk for later alcohol use disorder.

Second, it is possible that alcohol exposure during adolescence actually may alter neurodevelopmental processes in such a way that the likelihood of later abuse is increased. For example, alcohol use could promote rewiring or alter normal maturation and pruning within the nervous system. Ample evidence exists that exposing rats to low or moderate doses of alcohol during the prenatal or early postnatal period yields a greater preference for ethanol's odor and its consumption later in life. The young rat's response to alcohol also is mediated by social factors such as maternal interactions and/or nursing from an intoxicated dam. Recent evidence shows that prior nursing experience from an ethanol-intoxicated dam heightens ethanol consumption in infant and adolescent rats. In contrast, relatively few reports using animal models to study the effects of adolescent alcohol exposure on later alcohol consumption exist, and the results are conflicting. Yet, as is the case with younger animals, social experiences associated with adolescent drinking may influence future drinking behaviors. More studies are needed, however, to explore whether a causal relationship between early chronic exposure to alcohol and later alcohol problems exists, as well as to discover the underlying mechanisms for this effect. Nonhuman primates, because of their extended adolescent period, offer a good opportunity to study the effects of early exposure to alcohol.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.