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Published on: August 18, 2008
Lack of mu-opioid receptor leads to an increase in the NMDA receptor subunit mRNA expression and NMDA-induced
1Department of Pharmacology, College of Pharmacy, Sungkyunkwan University, 440-746, Suwon, South Korea.
Abstract:
The present study investigated in situ hybridization of N-methyl-D-aspartate (NMDA) receptor (NR) subunit mRNA and convulsion induced by intracerebroventricular injection of NMDA, in order to examine changes in NMDA receptor function in mu-opioid receptor gene knockout mice. Levels of NR1 and NR2A subunit mRNA were significantly increased in the parietal cortex (8.4 and 10.6%, respectively) and hypothalamus (8.7 and 15.2%, respectively) in mu-opioid receptor knockout mice. Levels of NR2B subunit mRNA were noted to be increased in the parietal cortex (9.1%), thalamus (7.7%), and hypothalamus (10.4%) in mu-opioid receptor knockout mice. The ED(50) for NMDA-induced convulsion in wild-type mice was 0.20 microg/10 microl/mouse. The ED(50) in mu-opioid receptor knockout mice was 0.14 microg/10 microl/mouse. There is a significant difference in the potency ratio of wild-type mice versus knockout mice (potency ratio: 1.44, P < 0.05). These results indicate that mu-opioid receptor knockout mice are more sensitive to NMDA-induced convulsion. Therefore, these results suggest that absence of mu-opioid receptor gene is accompanied by changes in the NMDA receptor system which can modulate the synaptic excitability in the process such as convulsion or epilepsy.
Insights
Mu-opioid receptor knockout mice exhibit heightened sensitivity to N-methyl-D-aspartate (NMDA) induced seizures. This suggests that the absence of the mu-opioid receptor gene alters the NMDA receptor system, impacting synaptic excitability and potentially influencing conditions like epilepsy.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- The mu-opioid receptor system plays a role in modulating neuronal excitability.
- N-methyl-D-aspartate (NMDA) receptors are critical ionotropic glutamate receptors involved in synaptic plasticity and excitability.
- Understanding the interplay between opioid receptors and NMDA receptors is crucial for neurological research.
Purpose of the Study:
- To investigate the functional changes in the NMDA receptor system in mu-opioid receptor gene knockout mice.
- To determine if the absence of mu-opioid receptors affects susceptibility to NMDA-induced convulsions.
Main Methods:
- In situ hybridization was used to quantify NMDA receptor subunit mRNA levels in specific brain regions of knockout and wild-type mice.
- Intracerebroventricular injection of NMDA was employed to induce convulsions, and dose-response relationships (ED50) were determined.
Main Results:
- Mu-opioid receptor knockout mice showed significant increases in NR1, NR2A, and NR2B subunit mRNA levels in various brain regions, including the parietal cortex, thalamus, and hypothalamus.
- The ED50 for NMDA-induced convulsions was significantly lower in knockout mice compared to wild-type mice, indicating increased sensitivity.
- Potency ratio analysis confirmed a 1.44-fold higher sensitivity to NMDA-induced convulsions in mu-opioid receptor knockout mice (P < 0.05).
Conclusions:
- The absence of the mu-opioid receptor gene is associated with alterations in the NMDA receptor system.
- These changes in the NMDA receptor system in knockout mice lead to increased sensitivity to NMDA-induced convulsions.
- The findings suggest a modulatory role of the mu-opioid receptor system on NMDA receptor function, impacting synaptic excitability relevant to conditions like epilepsy.
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