TL neuro

July 10, 2014

Cognitive deficits produced by chronic alcohol drinking

Filed under: Alcohol, CANTAB, Discrimination/Reversal Learning — mtaffe @ 11:24 am

A new paper from the laboratory is now in press in print:

M. Jerry Wright, Jr and Michael A Taffe, Chronic periadolescent alcohol consumption produces persistent cognitive deficits in rhesus macaques. 2014, Neuropharmacology, 86:78-87. DOI: 10.1016/j.neuropharm.2014.07.003 [Publisher]

Although human alcoholics exhibit lasting cognitive deficits, it can be difficult to definitively rule out pre-alcohol performance differences. For example, individuals with a family history of alcoholism are at increased risk for alcoholism and are also behaviorally impaired. Similarly, a sample of 18-22 year-old men indicated that those who drank alcohol on a daily basis had the lowest IQ of any group examined. It has been shown that better cognitive function at the time of treatment predicts abstinence in alcoholics.

Wright-Cog2-Fig4discrimlearningAnimal models of controlled alcohol exposure permit balanced group assignment, thereby ruling out the effects of pre-existing differences. We have developed a model in which periadolescent male rhesus monkeys consume alcohol in short daily sessions, five days per week, for many months (see Additional Reading, below). This permits the longitudinal assessment of cognition and behavior throughout a course of chronic exposure to, and withdrawal from, alcohol. The group mean intake over the course of this study was 1.38 g of alcohol per kilogram bodyweight, which corresponds to just over 5 standard drinks consumed in an hour each day. The individual range was from 0.74 g/kg (3 standard drinks) to 1.93 g/kg (almost 8 standard drinks). Again, consumed over an hour. We interpret this as being consistent with binge drinking but note that many human alcoholics maintain high blood alcohol levels across most of the waking day.

In this new paper, a group of 5 monkeys consumed alcohol over the course of 10 months (200 sessions) and were then withdrawn from chronic alcohol. A parallel control group of 5 monkeys drank the Tang vehicle only. We show here a lasting deficit in the 24-hour retention of a learned discrimination when animals were. In this task, animals determine which of two different stimuli is associated with reward by trial-and-error responding. Once they made a criterion of 12 out of 15 correct responses, they were deemed to have learned the discrimination. We present data as the percentage of correct responses as well as the number of errors (square root transformed to normalize the variance in this figure) made prior to reaching criterion. Animals were evaluated on the same discrimination a day later and control subjects exhibited a performance savings (increased accuracy, reduced errors to criterion) which indicates some retention of what they had learned the day before. The chronic alcohol / 6-week withdrawn monkeys showed no such savings, as if they had no recollection of the prior day’s session.

This part of the study shows that lasting cognitive deficits are caused by chronic binge-level alcohol consumption over the course of 10 months. The treatment groups were matched on alcohol preference and behavioral capability prior to the assignment to chronic alcohol or vehicle conditions. Thus, we can rule out the role of pre-existing differences to a larger extent than is possible in human studies.

Crean et al. (2011): Chronic alcohol consumption impairs visuo-spatial associative memory in periadolescent rhesus monkeys.
Taffe et al. (2010): Long-lasting reduction in hippocampal neurogenesis by alcohol consumption in adolescent nonhuman primates.
Katner et al. (2007): Robust and Stable Drinking Behavior Following Long-Term Oral Alcohol Intake In Rhesus Macaques
Katner et al. (2004): Controlled and Behaviorally Relevant Levels of Oral Ethanol Intake in Rhesus Macaques Using a Flavorant-Fade Procedure
This work was supported by USPHS / NIH grants R01 AA016807 and R01 DA035482; Dr. Wright was supported by training grant T32 AA007456.


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