Behavioral Toxicology of Cognition: Extrapolation from Experimental Animal Models to Humans

• Type of Material: Article
• Authors: Merle G. Paule, National Center for Toxicological Research; Leonard Green, Washington University in St. Louis; Joel Myerson, Washington University in St. Louis; Maria Alvarado, Emory University; Jocelyne Bachevalier, Emory University; Jay S. Schneider, Thomas Jefferson University; Susan L. Schantz, University of Illinois
• Language: English
• Date: 2012-03-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Published by Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ntt.2012.01.008
• Title of Journal or Parent Work: Neurotoxicology and Teratology
• ISSN: 0892-0362
• Volume: 34
• Issue: 2
• Start Page: 263
• End Page: 273
• Grant/Funding Information: Grant sponsor: NIMH; Grant Number: MH-58846; Grant Sponsor: NICHD; Grant Number: HD-35471; Grant Sponsor NIH; Grant Number MH-055308, RR-00165.; The findings and conclusions in the report by M.G. Paule are those of the author and do not necessarily represent the views of the FDA and mention of trade names or commercial products does not constitute endorsement or recommendation for use.
• Keywords: Animals; Neuropsychological Tests; Behavior, Animal; Humans; Rats; Haplorhini; Memory; Disease Models, Animal; Parkinson Disease; Cognition; Cognition Disorders
• Research Categories: Biology, Neuroscience; Psychology, General

Abstract

A variety of behavioral instruments are available for assessing important aspects of cognition in both animals and humans and, in many cases, the same instruments can be used in both. While nonhuman primates are phylogenetically closest to humans, rodents, pigeons and other animals also offer behaviors worthy of note. Delay Discounting procedures are as useful as any in studies of impulsivity and may have utility in shedding light on processes associated with drug abuse. Specific memory tests such as Visual Paired Comparisons tasks (similar to the Fagan test of infant intelligence) can be modified to allow for assessment of different aspects of memory such as spatial memory. Use of these and other specific memory tasks can be used to directly monitor aspects of cognitive development in infant animals, particularly in nonhuman primates such as monkeys, and children and to draw inferences with respect to possible neuroanatomical substrates sub-serving their functions. Tasks for assessing working memory such as Variable Delayed Response (VDR), modified VDR and Spatial Working Memory tasks are now known to be affected in Parkinson's disease (PD). These and other cognitive function tasks are being used in a monkey model of PD to assess the ability of anti-Parkinson's disease therapies to ameliorate these cognitive deficits without diminishing their therapeutic effects on motor dysfunction. Similarly, in a rat model of the cognitive deficits associated with perinatal exposure to polychlorinated biphenyls (PCBs), clear parallels with children can be seen in at least two areas of executive function: cognitive flexibility and response inhibition. In the rat model, discrimination reversal tasks were utilized to assess cognitive flexibility, a function often assessed in humans using the Wisconsin Card Sorting Task. Response inhibition was assessed using performance in a Differential Reinforcement of Low Response Rates (DRL) task. As the data continue to accumulate, it becomes more clear that our attempts to adapt animal-appropriate tasks for the study of important aspects of human cognition have proven to be very fruitful.