The attention set-shifting test is sensitive for revealing sex-based impairments in executive functions following developmental lead exposure in rats

• Published in: Behavioural brain research Vol. 366; pp. 126 - 134
• Main Authors: Neuwirth, Lorenz S., Masood, Sidrah, Anderson, David W., Schneider, Jay S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 02.07.2019
• Subjects: Animals; Attention - drug effects; Attention - physiology; Attention set-shifting test; Cognitive flexibility; Developmental lead exposure; Dimensional shifts; Disease Models, Animal; Dysexecutive functions; Executive Function - drug effects; Executive Function - physiology; Female; Frontoexecutive functions; Hippocampus - metabolism; Lead - adverse effects; Lead Poisoning - metabolism; Male; Memory Disorders - metabolism; Rats; Rats, Long-Evans; Sex Factors; Attention set-shifting test; Developmental lead exposure; Frontoexecutive functions; Dimensional shifts; Cognitive flexibility; Dysexecutive functions
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2019.03.022

•Control male & female rats had similar ASST performance and frontoexecutive dysfunctions in Pb-exposed rats were observed.•Developmental Pb-exposure causes sex-based and time-period differences in ASST performance.•EPN and PERI Pb-exposures cause different sex-based ASST learning deficits.•EPN males could not complete the ASST, while PERI males could with delays.•EPN and PERI females required twice as many trials to complete the ASST. The literature on lead (Pb) exposure has focused in large part on hippocampal-based learning and memory deficits, although frontoexecutive dysfunctions are known to exist in Pb-exposed humans. This study examined the effects of perinatal (PERI) and early postnatal (EPN) developmental low-level Pb-exposures in rats on frontoexecutive functions, using the Attention Set-Shift Test (ASST). Control males and females performed the ASST similarly. Male EPN rats had difficulty with simple discrimination (SD) of odors and failed to complete the compound discrimination (CD) stage of the ASST. All other Pb-exposed rats completed the training and testing. Male PERI rats performed worse on the SD, intradimensional (ID), and intradimensional-reversal (ID-Rev) ASST stages when compared to male Control rats. Female EPN rats performed similar to Controls on the ID-Rev rats, whereas PERI rats performed better the trials-to-criterion on the ID-Rev than EPN and Control rats. Pb-exposed female rats had significant difficulty performing the ED/ED-Rev stages, with the number of trials-to-criterion double that required by Pb-exposed and Control male rats and Control female rats. Together, the ASST results showed that developmental Pb-exposure induces frontoexecutive dysfunction that persists into adulthood, with different sex-based vulnerabilities dependent upon the time-period of neurotoxicant exposure.