Lack of μ-opioid receptor leads to an increase in the NMDA receptor subunit mRNA expression and NMDA-induced convulsion

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 ED50 for NMDA-induced convulsion in wild-type mice was 0.20 mug/10 mul/mouse. The ED5(0) in mu -opioid receptor knockout mice was 0.14 mug/10 mul/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. (C) 2001 Elsevier Science BY All rights reserved.