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Competitive and non-competitive NMDA receptor antagonists in spatial learning tasks
1Department of Pharmacology, Merz & Co, Frankfurt/Main, F.R.G.
European Journal of Pharmacology
|March 24, 1992
Summary
Competitive N-methyl-D-aspartate (NMDA) receptor antagonists, CGP37849 and CGP39551, at low doses did not impair spatial learning in rats. However, high doses of these compounds and dizocilpine impaired spatial orientation and memory acquisition.
Area of Science:
- Neuroscience
- Pharmacology
- Cognitive Science
Background:
- N-methyl-D-aspartate (NMDA) receptors play a crucial role in synaptic plasticity and learning.
- NMDA receptor antagonists are investigated for their potential therapeutic effects and their impact on cognitive functions.
Purpose of the Study:
- To evaluate the effects of competitive (CGP37849, CGP39551) and non-competitive (dizocilpine) NMDA receptor antagonists on spatial learning and memory in rats.
- To determine dose-dependent effects of these antagonists on different aspects of spatial orientation and task acquisition.
Main Methods:
- Rats were trained on spatial orientation tasks in an 8-arm radial maze.
- Animals received intraperitoneal injections of CGP37849, CGP39551, or dizocilpine at various doses.
- Locomotor activity, spatial orientation, and acquisition of egocentric and allocentric tasks were assessed.
Main Results:
- Dizocilpine increased locomotor activity, while CGP compounds did not affect it at tested doses.
- High doses of CGP37849, CGP39551, and dizocilpine impaired the acquisition of spatial orientation and reversal learning.
- Low doses of CGP37849 and CGP39551, effective for anticonvulsant and anticataleptic effects, did not produce amnesic effects.
Conclusions:
- Competitive NMDA receptor antagonists (CGP37849, CGP39551) exhibit a dose-dependent effect on spatial learning, with low doses being behaviorally safe.
- Non-competitive NMDA receptor antagonist dizocilpine induced amnesic effects across its entire behaviorally effective dose range.
- These findings highlight the differential impact of competitive versus non-competitive NMDA receptor antagonism on cognitive processes like spatial memory.