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MK-801 induced amnesia for the elevated plus-maze in mice
1Institute of Physiology, Academy of Sciences of the Czech Republic, Vijdenska 1083, 142 20 4, Prague, Czech Republic.
Abstract:
MK-801, a non-competitive NMDA receptor antagonist, has been shown to have amnesic properties in animal models. The purpose of the present study was to examine potential amnesic effects of MK-801 in mice using the modified elevated plus-maze paradigm. An animal was placed on the distal end of an open arm, and the transfer latency, i.e. the time in which it moves to the enclosed arm, was measured. Four different experimental schedules (i.e. the combination of the treatment and the testing) were used: MK-801 (0.075, 0.15, 0.25 and 0.4 mg/kg or saline) were given (a) 30 min before the acquisition session, (b) immediately after the acquisition session, (c) 60 min after the acquisition session, and (d) 30 min before the retention session. The retention session always followed 24 h after the acquisition session. Analysis of data showed a significant shortening of the transfer latency in saline-treated animals during the retention session. Further, MK-801 (at the dose range of 0.15--0.4 mg/kg) administered before and immediately after the acquisition session as well as before the retention session prolonged the transfer latency during the retention session. In fact, transfer latencies in MK-801 treated mice did not differ from those measured during the acquisition session. Thus, prolongation of the transfer latency in MK-801-treated mice indicates deficits in 'memorization' processes. On the contrary, MK-801 given 60 min after the acquisition session failed to increase the transfer latency, which suggests that the memory trace was sufficiently consolidated at this time. Based on the present results, the glutamatergic NMDA receptor mechanisms play an important role in a spatial orientation of mice placed on the elevated plus-maze.
Insights
MK-801, an NMDA receptor antagonist, impairs memory in mice when administered before or immediately after learning. However, it does not affect memory consolidation when given 60 minutes post-learning, indicating NMDA receptor involvement in spatial memory formation.
Area of Science:
- Neuroscience
- Pharmacology
- Animal Behavior
Background:
- NMDA receptor antagonists, like MK-801, are known to induce amnesic effects in animal models.
- Understanding the role of NMDA receptors in memory processes is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the amnesic effects of MK-801 on spatial memory in mice.
- To determine the critical time window for NMDA receptor involvement in memory consolidation using the elevated plus-maze paradigm.
Main Methods:
- Mice were treated with varying doses of MK-801 or saline at different time points relative to acquisition and retention sessions.
- Spatial memory was assessed using the modified elevated plus-maze, measuring transfer latency.
- Four experimental schedules were employed to evaluate MK-801's impact on memory acquisition, consolidation, and retrieval.
Main Results:
- MK-801 administration (0.15–0.4 mg/kg) before or immediately after acquisition, and before retention, significantly prolonged transfer latency, indicating memory impairment.
- MK-801 given 60 minutes after acquisition did not affect transfer latency, suggesting memory consolidation was complete.
- Saline-treated animals showed a significant decrease in transfer latency during retention, indicating normal memory recall.
Conclusions:
- Glutamatergic NMDA receptor mechanisms are critical for spatial orientation and memory formation in mice.
- MK-801 disrupts memory processes when administered during or before the critical memory consolidation period.
- These findings highlight the temporal sensitivity of NMDA receptor function in memory consolidation.