A Key Tool for Learning & Memory Studies in Developmental & Reproductive Toxicology
At the recent 2025 Society of Toxicology (SOT) conference, Sarah Beck [https://www.linkedin.com/in/sarah-beck-993371114] and her team from Labcorp (Labcorp Eye and Harrogate, UK) presented fresh work on optimising and standardising the Morris Water Maze (MWM). This test is a cornerstone of learning and memory (L&M) assessments in developmental and reproductive toxicology (DART) studies – helping researchers evaluate how certain chemicals may impact neurodevelopment.
What is the Morris Water Maze?
Every time you re-trace your steps to find your car keys or navigate your way through a new city using landmarks, you’ve used spatial memory – the cognitive process the MWM is designed to test. In this experiment, animals swim in a pool to locate a hidden platform using visual cues around them. When tested across multiple days with the platform in the same place, the MWM also assesses reference memory, our ability to consistently recall information over time. Since these processes are closely linked to the hippocampus (the seahorse-shaped brain region heavily involved in learning, memory and spatial navigation), the MWM provides valuable insight into brain development and function (depending on the age of the animal tested).
Why Optimise the MWM?
Regulatory toxicology studies that assess learning and memory must meet strict guidelines, including for some demonstration that the method is sensitive (for example, EPA and OECD developmental neurotoxicity studies). This is done via the use of positive and negative control data i.e., data that demonstrate the test reliably measures both what untreated ‘normal’ is, and what happens when the animals are exposed to a substance known to cause issues. The team’s work aimed to fine-tune the MWM by validating and optimising the evaluation – ensuring it is both reliable and standardised for regulatory submissions.
The study examined two common rat strains (Wistar and Sprague Dawley), two age groups (juvenile and mature, at 24 and 63 days old, respectively), and two water temperatures (23°C and 29°C). The results: Beck and colleagues were able to demonstrate the effectiveness of the controls, with positive controls leading to deficiencies in spatial and reference learning. They were also able to demonstrate that animals exposed to room temperature water (23˚C) learned better than those in the higher temperature maze, as they were motivated to complete the task by the colder water. Importantly, the younger animals were able to complete the study and were not otherwise negatively impacted by the temperature, which is especially important when considering their comparatively greater vulnerability at 24 days old.
The Toxicology Regulatory Landscape & Why This Matters?
In recent years, some decisions issued by the EU Chemicals Agency ECHA included very specific recommendations for L&M assessments (including the MWM) using young animals (25 days old ±2 days) within studies that would not normally include these evaluations such as the extended one generation reproductive toxicity study (EOGRTS). Whilst such recommendations raise a number of concerns relating to animal welfare, practicalities and interpretation which remain valid, the evidence presented from the Labcorp team offers promising evidence on young animals’ ability to take part in these studies without negative impacts on their welfare.
Learn More About the Morris Water Maze
If you’re interested in diving deeper into this research, you can request a copy of “Optimising the Morris Water Maze as one of the key learning and memory assessments within developmental and reproductive toxicology (DART) studies” here: https://forms.zuant.com/forms/ft4AIOflEe%2Bm%2BH1pp6tmFg%3D%3D.
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