Related Experiment Video
Updated: Aug 24, 2026
Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
Chronic memantine does not block 3-nitropropionic acid-delayed ischaemic tolerance in rat hippocampal slices ex vivo
Tadeusz Frankiewicz1, Chris G Parsons
1Department of Preclinical Research & Development, Merz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, 60318 Frankfurt/Main, Germany.
Abstract:
The moderate affinity uncompetitive NMDA receptor antagonist memantine, at concentrations found to be neuroprotective in animal models of chronic excitotoxicity, did not reduce ischaemic tolerance induced chemically with 3 nitropropionic acid (3-NP), but actually tended to enhance this effect ex vivo. Injection of 3-NP (20 mg/kg i.p.)--24 h prior to the in vitro experiment--significantly protected against hypoxia/hypoglycaemia-induced suppression of extracellular field excitatory postsynaptic potentials (fEPSPs) in rat hippocampal slices (62.2% vs. control of 16.8%), whereas 3 days pre-treatment with memantine (20 mg/kg/day--Alzet minipumps) tended to enhance recovery further following 3-NP preconditioning (89.7%). This low dose of memantine had no effect on fEPSPs in the absence of preconditioning. As expected, 3 days pre-treatment with a high dose of (+)MK-801 (dizocilpine; 2 mg/kg/day--Alzet minipumps) tended to reduce ischaemic tolerance following 3-NP preconditioning (45.3%). We conclude that although NMDA receptors do seem to be involved in chemically-induced ischaemic tolerance, semi-chronic pre-treatment with therapeutically-relevant doses of memantine does not block ischaemic tolerance.
Insights
Memantine, an NMDA receptor antagonist, did not reduce chemically-induced ischemic tolerance in rat brain slices. Therapeutically relevant doses of memantine even tended to enhance this neuroprotective effect.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Ischemic tolerance is a neuroprotective state against neuronal damage.
- N-methyl-D-aspartate (NMDA) receptors play a role in excitotoxicity and neuronal plasticity.
Purpose of the Study:
- To investigate the effect of memantine, an NMDA receptor antagonist, on chemically induced ischemic tolerance.
- To determine if therapeutically relevant doses of memantine block neuroprotection against hypoxia/hypoglycemia.
Main Methods:
- Induction of ischemic tolerance using 3-nitropropionic acid (3-NP) in rat hippocampal slices.
- Assessment of extracellular field excitatory postsynaptic potentials (fEPSPs) suppression.
- Pre-treatment with memantine or (+)MK-801 via Alzet minipumps.
Main Results:
- 3-NP preconditioning significantly protected against hypoxia/hypoglycemia-induced fEPSP suppression (62.2%).
- Memantine pre-treatment (20 mg/kg/day) tended to enhance recovery further (89.7%) without affecting basal fEPSPs.
- (+)MK-801 pre-treatment (2 mg/kg/day) reduced ischemic tolerance (45.3%).
Conclusions:
- NMDA receptors are involved in chemically-induced ischemic tolerance.
- Semi-chronic pre-treatment with therapeutically relevant doses of memantine does not block, but may enhance, ischemic tolerance.
More Related Videos
09:51Recording Synaptic Plasticity in Acute Hippocampal Slices Maintained in a Small-volume Recycling-, Perfusion-, and Submersion-type Chamber System
Published on: January 1, 2018
09:39Improved Preparation and Preservation of Hippocampal Mouse Slices for a Very Stable and Reproducible Recording of Long-term Potentiation
Published on: June 26, 2013