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Related Experiment Video

Updated: May 9, 2026

Assessing Spatial Memory Impairment in a Mouse Model of Traumatic Brain Injury Using a Radial Water Tread Maze
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Memantine protects rats treated with intrathecal methotrexate from developing spatial memory deficits.

Peter D Cole1, Veena Vijayanathan, Nafeeza F Ali

  • 1Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461, USA. Peter.Cole@Einstein.YU.edu

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|July 9, 2013
PubMed
Summary

Memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist, prevents cognitive deficits in rats treated with methotrexate. This suggests memantine may benefit cancer patients receiving methotrexate chemotherapy.

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Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Methotrexate chemotherapy can cause cognitive deficits.
  • Elevated homocysteic acid (HCA) is linked to methotrexate-induced memory impairment.

Purpose of the Study:

  • To determine if memantine can prevent methotrexate-induced cognitive deficits.
  • To investigate the mechanism of memantine's protective effect.

Main Methods:

  • Administered intrathecal methotrexate to rats, inducing spatial memory deficits.
  • Tested if intrathecal homocysteic acid (HCA) replicated memory deficits.
  • Assessed memantine's protective effect against methotrexate-induced deficits.
  • Examined memantine's impact on NMDA receptor expression and neurotransmitter levels.

Main Results:

  • Methotrexate induced lasting spatial memory deficits.
  • Intrathecal HCA reproduced these memory deficits.
  • Memantine reduced the incidence of methotrexate-induced deficits from 56% to 20%.
  • Memantine did not alter NMDA receptor expression or HCA/glutamate levels.

Conclusions:

  • Excitotoxic glutamate analogs like HCA contribute to methotrexate-induced cognitive deficits.
  • Memantine, an NMDA receptor antagonist, reduces these deficits.
  • Memantine shows potential therapeutic benefit for cancer patients undergoing methotrexate treatment.