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Effects of an NMDA-receptor antagonist MK-801 on an MMN-like response recorded in anesthetized rats
Dmitry Tikhonravov1, Tuomas Neuvonen, Antti Pertovaara
1Neuroscience Unit, Institute of Biomedicine/Physiology, University of Helsinki, Finland; Helsinki Brain Research Center, Finland.
Abstract:
In the human brain, auditory sensory memory has been extensively studied using a well-defined component of event-related potential named the mismatch negativity (MMN). The MMN is generated in the auditory and frontal cortices in response to deviant stimuli. In monkeys, cortical N-methyl-d-aspartate (NMDA) receptors have a central role in the generation of the MMN. MMN-like responses have also been recorded in other animals, including rats. The present study aimed at determining whether the MMN-like response in rats depends on an intact NMDA-receptor system. We recorded auditory evoked responses during an oddball paradigm epidurally in anesthetized rats that had received intraperitoneal injections of saline or an NMDA-receptor antagonist MK-801. An MMN-like response was recorded in the oddball paradigm in saline-treated rats. Further, this response was dose-dependently blocked by MK-801. These results suggest that the MMN-like response in rats depends on an intact NMDA-receptor system.
Insights
Auditory sensory memory, measured by mismatch negativity (MMN), relies on N-methyl-d-aspartate (NMDA) receptors in rats. Blocking NMDA receptors with MK-801 dose-dependently inhibited the MMN-like response in this study.
Area of Science:
- Neuroscience
- Auditory Perception
- Neuropharmacology
Background:
- Auditory sensory memory in humans is studied via mismatch negativity (MMN), an event-related potential linked to auditory and frontal cortices.
- Cortical N-methyl-d-aspartate (NMDA) receptors are crucial for MMN generation in monkeys.
- MMN-like responses have been observed in rats, suggesting conserved neural mechanisms.
Purpose of the Study:
- To investigate the role of the NMDA-receptor system in generating MMN-like responses in rats.
- To determine if NMDA receptor blockade affects MMN-like responses in the rat auditory system.
Main Methods:
- Auditory evoked responses were recorded epidurally in anesthetized rats using an oddball paradigm.
- Rats received intraperitoneal injections of either saline or the NMDA-receptor antagonist MK-801.
- The effect of MK-801 on the MMN-like response was assessed in a dose-dependent manner.
Main Results:
- An MMN-like response was successfully recorded in saline-treated rats during the oddball paradigm.
- Administration of MK-801 resulted in a dose-dependent blockade of the MMN-like response.
- The findings indicate a significant impact of NMDA receptor antagonism on the MMN-like response.
Conclusions:
- The MMN-like response in rats is dependent on an intact NMDA-receptor system.
- This study supports the involvement of NMDA receptors in auditory sensory memory processing across species.
- NMDA receptor antagonists represent a potential pharmacological tool to modulate MMN-like responses in preclinical models.
