Thursday, 21 August 2003
This presentation is part of : Thursday Poster Sessions

PD-006 Behavioral Effects of Subchronic Memantine Treatment in APP/PS1 Double Mutant Mice Modeling Alzheimer’s Disease

Heikki Tanila1, Rimante Minkeviciene1, and Pradeep Banerjee2. (1) University of Kuopio, Kuopio, Finland, (2) Forest Laboratories, Jersey City, NJ, USA

Objective: Memantine, a moderate affinity, uncompetitive NMDA receptor antagonist, is approved in Europe and under investigation in the US for the treatment of Alzheimer's disease. This study sought to determine the effects of subchronic memantine dosing on spatial memory and other behaviors in APP/PS1 double mutant mice.

Design/Methods: Eight-month-old male C57BL/6J mice carrying mutated human APPswe and PS1 (A246E) genes (A/P, n=45) and their nontransgenic littermates (NT, n=36) were assigned to memantine or placebo. Memantine (30 mg/kg) was administered orally for 3 weeks in drinking water prior to testing. Motor and exploratory activities were assessed by an automated activity monitor with infrared detection. Social behavior was assessed by the intruder-induced aggression test. Spatial working memory was tested by spontaneous alternation in the T-maze and spatial long-term memory in the Morris water maze.

Results: Memantine had no effect on locomotor activity or aggressive behavior as measured by the activity and intruder tests in either A/P or NT mice. Memantine-treated A/P mice spent more time exploring the T-maze and took longer to complete the test than vehicle-treated A/P mice, but both achieved similar alternation scores. In NT mice, memantine slightly increased time to completion but did not affect alternation scores. Memantine significantly improved acquisition of the water maze in A/P mice without affecting swimming speed and reduced escape latency in NT mice.

Conclusion: Memantine improved spatial learning in A/P and NT mice, did not slow swimming speed, and did not reduce locomotor activity in the activity box. These data indicate that memantine improves cognition in APP/PS1 double transgenic mice.

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