Water Maze Testing to Identify Compounds for Cognitive Enhancement
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Abstract
The water maze task is widely used to evaluate spatial learning and memory in rodents. The basic paradigm requires an animal to swim in a pool until it finds a hidden escape platform. The animals learn to find the platform using extra?maze cues and, after several training trials, are able to swim directly to it from any starting location. Memory for the platform location is assessed by examining swimming behavior with the platform removed from the maze, while sensory, motor and motivational aspects of the task can be examined by making the platform visible to the animals. Described in this unit is the use of the water maze to identify rats with age?related spatial learning and memory impairments. The efficacy of potential pharmacological treatments for alleviating these deficits is then evaluated. This assay provides a means for studying the neurobiology of spatial learning and memory, and to identify potential pharmacotherapies for treating memory?impaired humans. While the use of aged rats is described in this unit, the protocol can also be employed for compound screening with other rodent models that have spatial learning and memory impairments, such as transgenic mouse models of Alzheimer's disease. Curr. Protoc. Pharmacol. 59:5.63.1?5.63.12. © 2012 by John Wiley & Sons, Inc.
Keywords: water maze; spatial memory; aging; cognition rodent
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- Introduction
- Strategic Planning
- Basic Protocol 1: Testing Cognition Enhancers Using Aged Rats in the Water Maze
- Commentary
- Literature Cited
- Figures
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Basic Protocol 1: Testing Cognition Enhancers Using Aged Rats in the Water Maze
Materials
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Figure 5.63.1 A typical water maze arrangement. The pool (1.6 m in diameter) is filled with water colored with nontoxic white latex paint. Large and distinctive visual cues are located around the pool. A rat is standing on the hidden escape platform. The animal's fur has been dyed black to simplify tracking. The camera for the tracking system is positioned over the pool. It is not visible in this picture. View Image -
Figure 5.63.2 (A ) Diagram of the water maze showing the position of the escape platform (light gray) and surrounding circle (dotted line) indicating the annulus‐40, a circular area 40 cm in diameter centered over the platform location, used as one potential measure in the analysis of probe trials. The crossed dashed lines indicate the imaginary division of the pool into four quadrants. Trial start positions (1‐3) are shown. (B ) Sequence of start position locations used during training. View Image -
Figure 5.63.3 (A ) Water maze training. Typical performances of young and aged male Fischer 344 rats in the water maze. Young rats quickly learn the location of the hidden platform. Old rats show varying levels of competence. Comparing the performance of individual aged animals to the mean for the young rats over the last three training days identifies populations of aged‐unimpaired (AU; <0.5 s.d. from the young group) and aged‐impaired (AI; >2.0 s.d. from the young group) animals. AI rats are used for subsequent evaluation of putative cognitive enhancers. (B ) Probe trial performances on day 5. Time spent in the annulus‐40 is significantly reduced in AI rats (top). The swim paths are not significantly different between groups (bottom), demonstrating that the reduced dwell time in the annulus‐40 by AI rats was not simply due to slower swim speed during the probe trial. n = 12 to 15 per group; * = p < 0.05 versus vehicle. View Image -
Figure 5.63.4 Compounds shown to improve spatial memory in AI rats. Values represent means for all trials over 3 consecutive days of testing. For the purposes of comparing relative efficacy, the results of the most effective dose of each compound are shown. Primary mechanisms of action: donepezil (acetylcholinesterase inhibitor); GTS‐21 (nicotinic cholinergic α7 partial agonist); SB271046 (serotonin 5‐HT6 antagonist); BIBN‐99 (muscarinic cholinergic m2 antagonist); AR‐R17779 (nicotinic cholinergic α7 full agonist); MEM 1003 (L‐type calcium channel blocker); RG3487 (nicotinic cholinergic α7 partial agonist). n = 6 to 10 per group; * = p < 0.05 versus vehicle. View Image
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