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.
Jang
C G
CG
Department of Pharmacology, College of Pharmacy, Sungkyunkwan University, 440-746, Suwon, South Korea.
Lee
S Y
SY
Loh
H H
HH
Ho
I K
IK
D000818:Animals; D004827:Epilepsy / Q000139:chemically induced / Q000235:genetics*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D015870:Gene Expression; D017403:In Situ Hybridization; D007276:Injections, Intraventricular; D051379:Mice; D018345:Mice, Knockout; D016202:N-Methylaspartate / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*
D018690:Excitatory Amino Acid Agonists; D016202:N-Methylaspartate; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D017450:Receptors, Opioid, mu; C120997:NR2A NMDA receptor