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Competitive and noncompetitive NMDA antagonists block sensitization to methamphetamine
T Ohmori1, T Abekawa, A Muraki
1Department of Psychiatry and Neurology, Hokkaido University School of Medicine, Sapporo, Japan.
Pharmacology, Biochemistry, and Behavior
|July 1, 1994
Summary
Both competitive and noncompetitive NMDA antagonists block behavioral sensitization to methamphetamine (MA). Repeated NMDA antagonist administration leads to tolerance, not cross-sensitization with MA.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Methamphetamine (MA) abuse is a significant public health concern.
- NMDA receptors play a crucial role in synaptic plasticity and learning.
- Understanding the mechanisms of MA sensitization is vital for developing effective treatments.
Purpose of the Study:
- To investigate the effects of competitive and noncompetitive NMDA antagonists on MA-induced behavioral sensitization.
- To examine the behavioral effects of repeated administration of NMDA antagonists.
- To determine potential cross-sensitization or tolerance between NMDA antagonists and MA.
Main Methods:
- Rats were administered escalating doses of MA to induce behavioral sensitization.
- Rats were pretreated with MK-801 (noncompetitive) or D-CPP-ene (competitive) NMDA antagonists before MA administration.
- Behavioral activity was monitored following drug challenges.
- Tolerance and cross-sensitization were assessed.
Main Results:
- NMDA antagonists (MK-801 and D-CPP-ene) prevented the development of MA-induced behavioral supersensitivity.
- Repeated administration of MK-801 or D-CPP-ene resulted in decreased motor activity upon subsequent challenge, indicating tolerance.
- No cross-sensitization was observed between MA and either NMDA antagonist.
Conclusions:
- Both competitive and noncompetitive NMDA receptor antagonists effectively block behavioral sensitization to methamphetamine.
- Repeated exposure to NMDA antagonists leads to the development of behavioral tolerance to their own effects.
- These findings highlight the critical role of NMDA receptor function in the neuroadaptations underlying stimulant sensitization.