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Tests for learning and memory in rodent regulatory studies.

Charles V Vorhees1, Michael T Williams1

  • 1Department of Pediatrics, University of Cincinnati College of Medicine and Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Current Research in Toxicology
|February 2, 2024
PubMed
Summary

Regulatory guidelines for assessing developmental neurotoxicity in rodents should include two learning and memory (L&M) tests. The Morris water maze (MWM) and Cincinnati water maze (CWM) are recommended for evaluating explicit and implicit L&M, respectively.

Keywords:
Cognitive flexibilityCognitive tests for safety studiesDevelopmental neurotoxicity guideline studiesEgocentric memoryLearning and memoryNeurobehavioral regulatory studiesProcedural memoryRatsSpatial memory

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Area of Science:

  • Neuroscience
  • Toxicology
  • Cognitive Science

Background:

  • Regulatory guidelines for developmental neurotoxicity assessment have historically relied on a single learning and memory (L&M) test in rodents.
  • Recent agency requests indicate a need for dual L&M testing to better evaluate higher cognitive functions.

Purpose of the Study:

  • To identify appropriate rodent L&M tests for regulatory safety studies assessing developmental neurotoxic potential.
  • To provide evidence-based recommendations for evaluating adverse brain effects related to chemical exposures.

Main Methods:

  • Review of the neurobiological basis of two critical L&M types: spatial (explicit) and egocentric (implicit).
  • Identification of brain regions mediating these L&M types: hippocampus/entorhinal cortex and striatum/related structures.
  • Evaluation of water maze tasks for their suitability in regulatory safety assessments.

Main Results:

  • Spatial L&M, mediated by the hippocampus, is assessed using the Morris water maze (MWM).
  • Egocentric/procedural L&M, mediated by the striatum, is assessed using the Cincinnati water maze (CWM).
  • Both MWM and CWM possess characteristics suitable for regulatory safety studies.

Conclusions:

  • Dual L&M testing, utilizing MWM and CWM, offers enhanced evidence-based protection against developmental neurotoxicity.
  • These specific water maze tasks are well-suited for regulatory guidelines due to their ability to assess distinct cognitive functions mediated by different brain regions.