NMDA receptor antagonists impair motor performance in immature rats
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- 2-Amino-5-phosphonovalerate analogs & derivatives pharmacology MeSH
- Excitatory Amino Acid Antagonists pharmacology MeSH
- Time Factors MeSH
- Behavior, Animal drug effects MeSH
- Dizocilpine Maleate pharmacology MeSH
- Rats MeSH
- Animals, Newborn MeSH
- Rats, Wistar MeSH
- Psychomotor Performance drug effects MeSH
- Receptors, N-Methyl-D-Aspartate antagonists & inhibitors MeSH
- Age Factors MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 2-amino-4-methyl-5-phosphono-3-pentenoic acid MeSH Browser
- 2-Amino-5-phosphonovalerate MeSH
- Excitatory Amino Acid Antagonists MeSH
- Dizocilpine Maleate MeSH
- Receptors, N-Methyl-D-Aspartate MeSH
RATIONALE: Antagonists of NMDA receptors are excellent anticonvulsants in adult animals but serious side effects prevent their clinical use. The effects of two antagonists on motor performance were studied to find out if they develop in parallel with previously described anticonvulsant action. METHODS: Motor performance of 12-, 18- and 25-day-old rats was studied using a battery of tests (surface righting, negative geotaxis, bar holding and wire mesh ascending and three age-specific tests). A competitive NMDA antagonist CGP 40116 (0.1, 0.5 and/or 1 mg/kg IP) and a noncompetitive one dizocilpine (0.1, 0.5 and/or 1 mg/kg IP) were tested. RESULTS: Ten minutes after CGP 40116, the performance was compromised in all tests but there was negative geotaxis in all age groups. A decrease in efficacy with age was clearly demonstrated. Righting ability remained untouched in 25-day-old animals. Dizocilpine also influenced the performance in all tests but righting (compromised only in the youngest group) when studied 10 min after the injection. The relation to age was not so marked as with CGP 40116. When the tests were applied 4 h after dizocilpine administration the results were similar to those at 10-min interval. Twenty-four hours after dizocilpine only cliff avoidance exhibited prolonged latencies in 12-day-old rats but significant effects were observed in 18-day-old (negative geotaxis, bar holding and wire mesh ascending) as well as 25-day-old animals (bar holding, jumping down with choice). CONCLUSIONS: The acute effects of both NMDA antagonists studied decreased with age; this age-related change was more marked with CGP 40116 than with dizocilpine. In contrast, duration of dizocilpine effects did not exhibit a clear developmental tendency.
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