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-aspartat e (NMDA) receptor (NR) subunit mRNA and convulsion induced by intracerebrov entricular 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 1 0.6%, respectively) and hypothalamus (8.7 and 15.2%, respectively) in mu -o pioid 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 con vulsion in wild-type mice was 0.20 mug/10 mul/mouse. The ED5(0) in mu -opio id 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 (po tency ratio: 1.44, P < 0.05). These results indicate that mu -opioid recept or knockout mice are more sensitive to NMDA-induced convulsion. Therefore, these results suggest that absence of mu -opioid receptor gene is accompani ed by changes in the NMDA receptor system which can modulate the synaptic e xcitability in the process such as convulsion or epilepsy. (C) 2001 Elsevie r Science BY All rights reserved.