Effects of the uncompetitive NMDA receptor antagonist memantine on hippocampal long-term potentiation, short-term exploratory modulation and spatial memory in awake, freely moving rats

Carol A Barnes, W. Danysz, C. G. Parsons

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119 Citations (Scopus)

Abstract

Chronic treatment of adult male F-344 rats (9-12 months old) with therapeutically relevant doses of memantine (30 mg/kg/day in chow for > 8 weeks) increased the maintenance of long-term potentiation of field excitatory postsynaptic potentials from perforant path-granule cell hippocampal synapses recorded in the fascia dentata in vivo. In contrast, there was no effect of memantine on baseline synaptic responses or population spikes. Likewise, short-term exploratory modulation of these hippocampal evoked responses was not different between memantine-treated and control rats. Both groups of rats were able to learn the spatial version of the Morris water task equally well, but the memantine-treated group showed a strong tendency to show more selective spatial search patterns in the training quadrant of the water pool during a final probe trial. As such, these studies provide the first electrophysiological evidence that memantine can increase the durability of synaptic plasticity and provide preclinical confirmation of the cognitive improvement seen with memantine in the treatment of demented patients.

Original languageEnglish (US)
Pages (from-to)565-571
Number of pages7
JournalEuropean Journal of Neuroscience
Volume8
Issue number3
DOIs
StatePublished - 1996

Fingerprint

Memantine
Long-Term Potentiation
N-Methyl-D-Aspartate Receptors
Perforant Pathway
Neuronal Plasticity
Water
Excitatory Postsynaptic Potentials
Dentate Gyrus
Synapses
Spatial Memory
Therapeutics
Population

Keywords

  • Chronic
  • Fascia dentata
  • Morris maze
  • Oral administration

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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AU - Parsons, C. G.

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