Memantine improves spatial learning in a transgenic mouse model of Alzheimer's disease


BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2004
Contact PI Name:
Heikki Tanila
Contact PI Affiliation:
Department of Neuroscience and Neurology, University of Kuopio, Finland
Co-Authors:
Rimante Minkeviciene, Pradeep Banerje
Primary Reference (PubMED ID):
Funding Source:
Forest Laboratories
Study Goal and Principal Findings:

The overarching aim of this report was to determine the effect of sub chronic oral administration of memantine on hippocampus-based spatial learning and other general behaviors in the APPswe/ PS1 transgenic mouse model of AD. Eight-month-old male transgenic mice, and their nontransgenic (NT) litter mates were orally administered a dose of memantine yielding therapeutic plasma concentrations of the drug and mimicking its clinical use. At this age, APP/PS1 mice show elevated levels of β-amyloid peptides in several brain regions. APP/PS1 mice exhibited less exploratory rearing and increased aggressive behavior compared with NT mice. In the water maze test for spatial learning, APP/PS1 mice had longer escape latencies to both hidden and visible platforms, but they did not differ from NT mice in their swimming speed.  Memantine significantly improved the acquisition of the water maze in transgenic mice (but not NT mice) without affecting swimming speed. Memantine did not affect either locomotor activity or aggressive behavior in either transgenic or NT mice. These data indicate that memantine improves hippocampus-based spatial learning in a transgenic mouse model of AD without producing nonspecific effects on locomotion/exploratory activity.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Memantine
Therapeutic Target:
NMDA Receptor

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1
Strain/Genetic Background:
C57BL/6J
Species:
Mouse
Model Type:
Non-transgenic
Strain/Genetic Background:
C57BL/6J

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Exploratory Activity
Isolation-Induced Aggression
Morris Water Maze
Pharmacokinetics
Drug Concentration-Plasma

Source URL: http://alzped.nia.nih.gov/memantine improves spatial