The Effects of Neurodevelopmental Lead Exposure on The NeuwirthTM Hole Board Test

Abstract

Rodent models are the primary species for pre-clinical study and experimentation for biomedical translational research. However, subsequent testing on a variety of behavioral tests as a "battery" can often result in an extraneous variable of confounding carryover effects if not carefully considered. For example, if a more stressful test is used prior to a less stressful test, inflated and artifactual increases in the latter test may be considered real. Thus, care behavioral test sequences are critical to avoid these pre-clinical testing errors that may forestall promising drug candidates for clinical phase trials. In the present study, we examined the NeuwirthTM Hole board test, which is designed to overcome these testing sequence confounds, by using the same testing apparatus over 2 days. In day 1, a 10 minute exploration trial is used to assess fear/escape behaviors. Then, 24 hrs later, 4 Petri Dishes with 4 different odors are placed below the apparatus to increase the rat's cognitive/exploratory behaviors and overcome both the prior day's anxiety-like behaviors and habituation over 2 days. We explored this testing procedure to evaluate the effects of neurodevelopmental lead exposure and how it may be a useful tool in parsing very subtle brain deficits through such a simple testing procedure. This is a pilot study that currently shows that the test can be used to determine both sex-dependent and developmental time-period differences in the rats behaviors. This testing procedure may have greater advantages for pre-clinical study that may further accelerate drug advancement to clinical phase trials.