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The effects of NMDA antagonists on punished exploration in mice
1Synthélabo Recherche (L.E.R.S.), 31 ave P.V. Couturier, 92220, Bagneux, France.
Abstract:
Previous studies have reported that several NMDA antagonists show anxiolytic-like activity in behavioural tests. To follow up the observation that AP7 increased the punished exploration of mice in the four plate test, several NMDA antagonists were tested in this procedure in shocked and non-shocked conditions. AP7 increased shocked exploration without increasing non-shocked exploration. However, another competitive NMDA antagonist, CGS 19755, produced no increases in exploration in either condition. The non-competitive antagonists, phencyclidine, MK-801 and dextromethorphan, produced dose-related increases in activity in both the non-shocked and shocked conditions. This effect is probably best considered a psychomotor stimulant action rather than an anxiolytic-like activity. The non-competitive NMDA antagonist, SL 82.0715, which acts at the polyamine site, and the ethyl ester of 7-chlorokynurenic acid, which acts at the glycine modulatory site, produced only decreases in exploration indicating that they lack both stimulant and anxiolytic activity. Although providing little evidence for anxiolytic action the present results further demonstrate that compounds acting at different sites within the NMDA receptor complex can give rise to very different pharmacological and behavioural effects.
Insights
NMDA antagonists exhibit varied effects on mouse behavior. While some show stimulant actions, others lack anxiolytic or stimulant activity, highlighting diverse NMDA receptor complex pharmacology.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- NMDA receptor antagonists have been previously linked to anxiolytic-like activity in behavioral tests.
- Previous observations indicated AP7 increased punished exploration in mice.
Purpose of the Study:
- To investigate the effects of various NMDA antagonists on mouse behavior in shocked and non-shocked conditions.
- To differentiate between anxiolytic and psychomotor stimulant effects of NMDA antagonists.
Main Methods:
- Utilized the four plate test to assess mouse exploration under shocked and non-shocked conditions.
- Administered different NMDA antagonists, including competitive (AP7, CGS 19755) and non-competitive (phencyclidine, MK-801, dextromethorphan, SL 82.0715) types, as well as a glycine site antagonist.
Main Results:
- AP7 increased exploration in shocked mice but not non-shocked mice.
- Non-competitive antagonists (phencyclidine, MK-801, dextromethorphan) dose-dependently increased activity in both conditions, suggesting psychomotor stimulant effects.
- CGS 19755 showed no effect on exploration. SL 82.0715 and the glycine site antagonist decreased exploration, indicating a lack of stimulant or anxiolytic activity.
Conclusions:
- The study provides limited evidence for anxiolytic actions of the tested NMDA antagonists.
- Different compounds acting on the NMDA receptor complex produce distinct pharmacological and behavioral outcomes.
- The site of action within the NMDA receptor complex significantly influences the observed behavioral effects.