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Effects of NMDA receptor-related agonists on learning and memory impairment in olfactory bulbectomized mice
T Tadano1, S Hozumi, F Yamadera
1Department of Pharmacology, Tohoku Pharmaceutical University, Sendai, Japan. tadano@tohoku-pharm.ac.jp
Abstract:
A significant impairment of learning and memory-related behavior was induced in mice on the 7th and 14th days after olfactory bulbectomy (OBX), as measured by a passive avoidance task. The involvement of the N-methyl-D-aspartate (NMDA) receptor ion-channel complex for learning and memory-related behavior impairment was examined by the intracerebroventricular administration of several NMDA receptor-related agonists and in combination with antagonists. The NMDA receptor agonist NMDA (1 ng/mouse) and the polyamine site agonist spermidine (1 micro g/mouse) improved learning and memory-related behavior impairment. In contrast, the glycine agonist D-cycloserine (0.2, 1 and 5 micro g/mouse) had no effect on learning and memory-related behavior impairment. The improved effects by NMDA and spermidine were reversed by the coadministration of D-APV, a competitive NMDA receptor antagonist, MK-801, an NMDA ion-channel blocker and ifenprodil, a polyamine site antagonist, respectively. These results suggest that the degeneration of NMDA receptors and polyamine sites in the NMDA receptor ion-channel complex may be involved in the OBX-induced impairment of learning and memory-related behavior.
Insights
Olfactory bulbectomy impairs learning and memory in mice. NMDA receptor agonists, NMDA and spermidine, improved memory, suggesting NMDA receptor degeneration contributes to this impairment.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Neuropharmacology
Background:
- Olfactory bulbectomy (OBX) in mice causes significant learning and memory deficits.
- The N-methyl-D-aspartate (NMDA) receptor ion-channel complex is crucial for cognitive functions like learning and memory.
Purpose of the Study:
- To investigate the role of the NMDA receptor ion-channel complex in OBX-induced learning and memory impairment.
- To examine the effects of NMDA receptor agonists and antagonists on cognitive function after OBX.
Main Methods:
- Mice underwent olfactory bulbectomy (OBX) and were tested on a passive avoidance task.
- Intracerebroventricular administration of NMDA receptor agonists (NMDA, spermidine, D-cycloserine) and antagonists (D-APV, MK-801, ifenprodil).
Main Results:
- OBX induced significant learning and memory impairment on days 7 and 14.
- NMDA (1 ng/mouse) and spermidine (1 µg/mouse) administration improved memory deficits.
- D-cycloserine showed no effect on memory impairment.
- The beneficial effects of NMDA and spermidine were blocked by D-APV, MK-801, and ifenprodil, respectively.
Conclusions:
- Degeneration of NMDA receptors and polyamine sites within the NMDA receptor ion-channel complex may underlie OBX-induced cognitive deficits.
- Targeting NMDA receptor pathways could be a therapeutic strategy for memory impairment.
