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Simple Protocol for Distinguishing Drug-induced Effects on Spatial Memory Acquisition, Consolidation and Retrieval in
Ariel K Frame1, Asad Lone1, Richard A Harris1
1Department of Biology, Western University, London, Ontario N6A 5B7, Canada.
Abstract:
The Morris water maze (MWM) is one of the most commonly used tests for assessing spatial learning and memory in mice. While the MWM is highly amenable to testing the effects of memory modifying drugs, most studies do not consider the timing or duration of drug exposure when conducting the MWM assay; factors that can strongly influence the effect of the drug on different stages of memory and interfere with data interpretation. Herein we describe a MWM protocol which offers the advantage of distinguishing the impact of a fast acting intraperitoneally (IP) injected drug on the different stages of spatial memory: acquisition, consolidation, and retrieval. Mice initially undergo habituation to both the MWM apparatus and IP injection procedure over the course of three days. For assessing the effect of a drug on memory acquisition, mice are injected with the drug prior to training sessions over four consecutive days, where mice learn to find an escape platform in a circular water tank using distal spatial cues. To determine the effect of the drug on memory consolidation, mice are injected with the drug immediately after each training session. For testing the effect of a drug on memory retrieval, mice receive mock IP injections on each training day and the drug is IP injected only once, prior to a probe trial, where mice attempt to locate the platform following its removal from the tank. This protocol provides a simple strategy for distinguishing the effect(s) of a CNS acting drug on the different stages of memory.
Insights
This study introduces a refined Morris water maze (MWM) protocol to precisely evaluate how drugs affect spatial memory acquisition, consolidation, and retrieval in mice. The method differentiates drug impacts on distinct memory stages for clearer data interpretation.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- The Morris water maze (MWM) is a standard tool for assessing spatial memory in mice.
- Current MWM studies often overlook drug administration timing, complicating the interpretation of memory-modifying drug effects.
- Understanding how drug timing influences memory stages is crucial for accurate pharmacological research.
Purpose of the Study:
- To present a modified MWM protocol for dissecting the effects of intraperitoneally (IP) injected drugs on specific stages of spatial memory.
- To enable researchers to distinguish between drug impacts on memory acquisition, consolidation, and retrieval.
Main Methods:
- Mice undergo habituation to the MWM and IP injections over three days.
- Drug effects on acquisition are assessed by IP injection before daily training over four days.
- Consolidation effects are studied via IP injection immediately after training sessions.
- Retrieval effects are evaluated by single IP injection before a drug-free probe trial.
Main Results:
- The protocol allows for the precise temporal differentiation of drug effects on spatial memory.
- It distinguishes whether a drug impacts learning (acquisition), memory storage (consolidation), or recall (retrieval).
Conclusions:
- This MWM protocol offers a straightforward strategy to analyze the impact of fast-acting, IP-administered drugs on distinct phases of memory.
- It enhances the interpretability of data in studies investigating central nervous system (CNS) acting drugs and memory.
