Aaron M. White

Cognitive deficits and CNS damage after a 4-day binge ethanol exposure in rats

Impairments of learning and memory are common neuropsychological sequelae of chronic alcohol abuse. Alcoholics often have impairments of anterograde memory, including spatial memory dysfunction, and a tendency toward response perseveration. This study was designed to assess the effects of binge ethanol exposure on neurodegeneration and cognitive function. Rats were given ethanol three times daily for 4 days. Silver staining revealed neurodegeneration in the olfactory bulb, piriform cortex, perirhinal cortex, entorhinal cortex, and dentate gyrus. After withdrawal, behavioral testing in the Morris water maze revealed significant differences in reversal learning between treatment groups. Ethanol-treated animals required more trials to learn the reversal task, entered the previously trained quadrant more often, and spent more time there than controls. [3H]PK-11195 binding, an index of CNS damage, was elevated in the piriform cortex of ethanol-treated animals. Thus, binge ethanol exposure resulted in neurodegeneration of a corticolimbic circuit with common excitatory inputs from the olfactory bulb and was associated with perseverative responding on a spatial learning task. These studies suggest that a single binge drinking episode could cause neurodegeneration and cognitive dysfunction in humans. The perseverative nature of the behavioral deficit could be related to both cognitive dysfunction and the behavioral components of the addiction process.

Adolescence: Booze, Brains, and Behavior

This article represents the proceedings of a symposium at the 2004 Research Society on Alcoholism meeting in Vancouver, British Columbia, Canada, organized and chaired by Peter M. Monti and Fulton T. Crews. The presentations and presenters were (1) Introduction, by Peter M. Monti; (2) Adolescent Binge Drinking Causes Life-Long Changes in Brain, by Fulton T. Crews and Kim Nixon; (3) Functional Neuroimaging Studies in Human Adolescent Drinkers, by Susan F. Tapert; (4) Abnormal Emotional Reactivity as a Risk Factor for Alcoholism, by Robert Miranda, Jr.; (5) Alcohol-Induced Memory Impairments, Including Blackouts, and the Changing Adolescent Brain, by Aaron M. White and H. Scott Swartzwelder; and (6) Discussion, by Kenneth Sher.

Ethanol, memory, and hippocampal function: a review of recent findings.

For well over a century, ethanol was believed to exert its effects on cognition and behavior by producing a ubiquitous depression of central nervous system activity. A general disruption in brain function was consistent with the belief that ethanols effects on cognition and behavior were also quite general. Substantial evidence now indicates that ethanol produces a host of selective effects on neural activity, resulting in regional differences in ethanols effects in the brain. Consistent with such evidence, recent research suggests that ethanols effects on cognition and behavior are not as global as previously assumed. The present paper discusses evidence that many of ethanols effects on learning and memory stem from altered cellular activity in the hippocampus and related structures. Potential mechanisms for ethanols disruption of hippocampal function are reviewed. Evidence suggests that ethanol disrupts activity in the hippocampus by interacting directly with hippocampal neurons and by interacting with critical hippocampal afferents. Hippocampus 2000;10:88–93.

Differential effects of ethanol on motor coordination in adolescent and adult rats.

Recent evidence suggests that adolescence represents a unique period of sensitivity to the effects of ethanol. Adolescent animals are more sensitive than adults to many of the effects of ethanol, including ethanol-induced learning and memory impairments, while being less sensitive to others, including ethanol-induced sedation. It is well known that ethanol produces dramatic impairments in balance and motor coordination. While previous research suggests that adolescents and adults do not differ in their sensitivity to the effects of relatively low doses of ethanol on motor coordination, it is not known whether differences in performance would emerge at higher doses. The present study compared the impact of a range of ethanol doses (1.0, 2.0 and 3.0 g/kg) on motor coordination in adolescent [postnatal day (PD) 35-40] and adult (PD 70-75) rats. Motor coordination was assessed using the tilting plane test before ethanol administration (baseline) and at 15, 30, 60, 120 and 180 min after ethanol administration. Performance was not affected by 1.0 g/kg ethanol in either age group. However, adults were more impaired than adolescents at nearly every time point following administration of both 2.0 and 3.0 g/kg ethanol. The results provide further evidence that adolescents and adults are differentially sensitive to the behavioral effects of ethanol. Given the critical role of motor coordination in the ability to operate motor vehicles and the central role of balance and coordination in field sobriety tests, these data could have important implications if extended to human subjects.

Hippocampal Function during Adolescence: A Unique Target of Ethanol Effects

Abstract: Behaviors mediated by the hippocampus have long been known to be sensitive to the acute, chronic, and prenatal effects of ethanol. It has recently become clear that hippocampal function is uniquely responsive to ethanol during periadolescent development, and that alcohol affects behavior and brain function differently in adolescents and adults. We have used behavioral techniques, as well as extracellular and whole‐cell electrophysiological techniques, to assess the effects of acute and chronic ethanol exposure on hippocampal function during adolescence and adulthood. Our results are consistent with the view that the hippocampus is more sensitive to the acute effects of ethanol during adolescence and may be more susceptible to the neurotoxic effects of ethanol during this developmental period. Studies of this type have yielded valuable information for prevention, education, and public policy efforts related to underage drinking.

Age-related effects of alcohol on memory and memory-related brain function in adolescents and adults.

As detailed in this brief review, there is now clear evidence that adolescence represents a unique stage of brain development. Changes in brain organization and function during adolescence are widespread, and include intense rewiring in the frontal lobes and other neorcortical regions, as well as changes in a litany of subcortical structures. Recent research suggests that, because of these changes in brain function, drugs like alcohol affect adolescents and adults differently. The available evidence, much of it from research with animal models, suggests that adolescents might be more sensitive than adults to the memory impairing effects of alcohol, as well as the impact of alcohol on the brain function that underlies memory formation. For instance, when treated with alcohol, adolescent rats perform worse than adults in spatial learning tasks that are known to require the functioning of the hippocampus. Alcohol disrupts hippocampal function, and does so more potently in adolescents than adults. In contrast, adolescents appear to be far less sensitive than adults to both the sedative and motor impairing effects of alcohol. While research on this topic is still in its infancy, the findings clearly suggest that adolescence represents a unique stage of sensitivity to the impact of alcohol on behavior and brain function.

Prevalence and correlates of alcohol-induced blackouts among college students: results of an e-mail survey.

Abstract The authors conducted an e-mail survey of 772 college students to learn more about their experiences with blackouts. Approximately half (51%) of those who had ever consumed alcohol reported they had experienced a blackout at some point in their lives, and 40% had experienced 1 in the year before the survey. Among those who drank in the 2 weeks before the survey, nearly 1 in 10 (9.4%) had experienced a blackout during that period. Many later learned that, during the blackout, they had vandalized property, driven an automobile, had sexual intercourse, or engaged in other risky behaviors. Experiencing 3 or more blackouts was associated with a variety of other experiences, including heavier drinking, lower grades, an earlier age of drinking onset, and having others express concerns about their drinking. The female students who reported blackouts during the 2 weeks before the survey drank far less than male students did during this time period, supporting the use of gender-specific definitions of risky drinking.

Differential effects of delta9-THC on learning in adolescent and adult rats.

Marijuana use remains strikingly high among young users in the U.S., and yet few studies have assessed the effects of delta9-tetrahydrocannabinol (THC) in adolescents compared to adults. This study measured the effects of THC on male adolescent and adult rats in the Morris water maze. In Experiment 1, adolescent (PD=30-32) and adult (PD=65-70) rats were treated acutely with 5.0 mg/kg THC or vehicle while trained on the spatial version of the water maze on five consecutive days. In Experiment 2, adolescent and adult rats were treated acutely with 2.5 or 10.0 mg/kg THC or vehicle while trained on either the spatial and non-spatial versions of the water maze. In Experiment 3, adolescent and adult rats were treated with 5.0 mg/kg THC or vehicle daily for 21 days, and were trained on the spatial and then the non-spatial versions of the water maze task four weeks later in the absence of THC. THC impaired both spatial and nonspatial learning more in adolescents than in adults at all doses tested. However, there were no long-lasting significant effects on either spatial or non-spatial learning in rats that had been previously exposed to THC for 21 days. This developmental sensitivity is analogous to the effects of ethanol, another commonly used recreational drug.

Prenatal choline exposure alters hippocampal responsiveness to cholinergic stimulation in adulthood

Manipulation of dietary choline levels during gestation results in enduring neurobehavioral changes in offspring that last into adulthood. Alterations of hippocampal function and memory are among the most striking changes. Depending upon the measures assessed, prenatal choline supplementation tends to promote excitatory synaptic efficacy in hippocampal circuits while prenatal choline deficiency diminishes it. However, the mechanisms underlying these changes remain unclear. Transverse hippocampal slices were prepared from adult offspring of dams fed choline supplemented, choline deficient, or control diets. We assessed paired-pulse inhibition, and excitatory synaptic responsiveness before and after activation of cholinergic receptors with Carbachol. Prenatally choline deficient animals yielded significantly fewer electrophysiological viable hippocampal slices than did animals from either of the other two treatment groups. Among the slices tested, there were no differences in paired pulse inhibition between the treatment groups. However, transient cholinergic activation resulted in a prolonged enhancement of the amplitude of the population EPSP (pEPSP) response in slices from prenatally choline supplemented animals. These results suggest that GABA receptor-mediated inhibition remains intact after prenatal choline manipulations, and that enhancement of the excitatory responsiveness of hippocampal circuits in slices from prenatally choline supplemented rats may be related in part to an increase in cholinergic tone within the CA1 circuit.

Do College Students Drink More Than They Think? Use of a Free‐Pour Paradigm to Determine How College Students Define Standard Drinks

RATIONALE Much of what is known about college drinking comes from self-report survey data. Such surveys typically ask students to indicate how many drinks they consume within a given period of time. It is currently unclear whether college students and researchers use similar operational definitions of a single drink. This information is critical given the widespread reliance on survey data for assessing the correlates and consequences of college drinking. OBJECTIVES This study investigated whether college students define standard drink volumes in a way that is consistent with the operational definitions commonly used by researchers. METHODS Students (n = 106) were administered an alcohol survey and then asked to perform three tasks. The tasks involved free-pouring fluid into empty cups of different sizes and estimating the volume of a single beer, a shot of liquor, or the amount of liquor in a mixed drink. The volumes poured by students then were compared with standards used in a well-known nationwide survey (i.e., 12 oz of beer and 1.25 oz of liquor in a shot or mixed drink). RESULTS In every cup size of every task, students overestimated how much fluid they should pour to create a standard drink. In all three tasks, the magnitude of the discrepancy increased with cup size. Collapsed across cup sizes, students overpoured shots by 26%, mixed drinks by 80%, and beer by 25%. When a more liberal serving size of liquor (1.5 oz) was used as the standard, the results of the mixed drink task remained unchanged. However, the volumes poured by students during the shot free-pour task differed from the standard in only one cup size. CONCLUSIONS The data suggest that college students drink more alcohol than indicated by their survey responses, raising questions about the validity of widely used alcohol surveys. Efforts to educate students about the alcohol content of standard drinks should be enhanced.