Lack of mu-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 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.