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Does dizocilpine (MK-801) selectively block the enhanced responsiveness to repeated amphetamine administration?
D S Segal1, R Kuczenski, S M Florin
1Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla 92093, USA.
Behavioral Neuroscience
|June 1, 1995
Summary
N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) interacts uniquely with amphetamine. MK-801 pretreatment potentiates locomotor sensitization to amphetamine, suggesting a role in stimulant-induced behavioral changes.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- N-methyl-D-aspartate (NMDA) receptors are implicated in stimulant sensitization.
- Understanding the interaction between NMDA receptor antagonists and psychostimulants is crucial for elucidating sensitization mechanisms.
Purpose of the Study:
- To investigate the role of NMDA receptors in the development of amphetamine-induced sensitization.
- To characterize the behavioral effects of combined dizocilpine (MK-801) and amphetamine administration.
Main Methods:
- Detailed behavioral analysis of locomotor and stereotyped components of stimulant response.
- Concurrent assessment of emergent sensitization phases.
- Acute and chronic administration of MK-801 and amphetamine in rodents.
Main Results:
- MK-801 (0.125 mg/kg) altered the acute locomotor response to amphetamine in a dose-dependent manner.
- Repeated MK-801 + amphetamine administration suppressed stereotyped behaviors.
- A potentiated locomotor sensitization to amphetamine challenge was observed after repeated coadministration.
Conclusions:
- MK-801 pretreatment does not block, but rather augments, the development of amphetamine-induced locomotor sensitization.
- This augmentation persists for at least 48 hours post-treatment.
- NMDA receptor antagonism may play a complex role in stimulant sensitization, leading to unique behavioral outcomes.