Chronic periadolescent alcohol consumption produces persistent cognitive deficits in rhesus macaques

摘要

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. Animal models of controlled alcohol exposure permit balanced group assignment, thereby ruling out the effects of pre-existing differences. Periadolescent male rhesus macaques (N = 5) consumed alcohol during 200 drinking sessions (M-F) across a 10-month period (mean daily alcohol consumption: 1.38 g/kg/day). A control group (N = 5) consumed a fruit-flavored vehicle during the same period. Spatial working memory, visual discrimination learning and retention and response time behavioral domains were assessed with sub-tests of the Monkey CANTAB (CAmbridge Neuropsychological Test Automated Battery). Spatial working memory performance was impaired in the alcohol group after 120 drinking sessions (6 mo) in a manner that depended on retention interval. The chronic alcohol animals were also impaired in retaining a visual discrimination over 24 hrs when assessed 6-8 weeks after cessation of alcohol drinking. Finally, the presentation of distractors in the response time task impaired the response time and accuracy of the chronic alcohol group more than controls after 6 months of alcohol cessation. Chronic alcohol consumption over as little as 6 months produces cognitive deficits, with some domains still affected after acute (6-8 wks) and lasting (6 mo) discontinuation from drinking. Animals were matched on alcohol preference and behavioral performance prior to exposure, thus providing strong evidence for the causal role of chronic alcohol in these deficits.