The role of NR2B containing NMDA receptor in place preference conditioned with morphine and natural reinforcers in rats.
It has been reported that N-methyl-D-aspartate (NMDA) receptor is implicated in drug addiction and antagonists of the NMDA receptor complex can inhibit the development and expression of conditioned place preference (CPP) induced by several addictive drugs, implying that this class of compounds might be considered as candidate for the treatment of substance abuse. To explore this possibility, it is important to evaluate whether the inhibitory effect of NMDA receptor antagonists would be confined to behaviors produced by drugs of abuse only, but not by natural reinforcers. According to the quantitative changes of NMDA receptor subunits, including NR1, NR2A, and NR2B, induced by diverse types of reinforcers, we chose NR2B subunit as the target of research. Experimental results showed that (1) an augmented expression of NR2B subunit was revealed by Western blotting in the nucleus accumbens (NAc) and the hippocampus in rats with CPP induced by morphine, but not by natural rewards such as food, novel environment and social interaction. (2) Ifenprodil, an antagonist highly selective for NR2B subunit of the NMDA receptor, produced a dose-dependent reduction in CPP induced by morphine and novel environment, but not that by food consumption and social interaction. Taking together, these findings suggested that NR2B containing NMDA receptor may be more involved with morphine reward rather than natural rewards, and that antagonism of NR2B may have a potential for the treatment of morphine abuse.
Ma
Yao-Ying
YY
Neuroscience Research Institute and Department of Neurobiology, Peking University Health Science Center, Key Laboratory of Neuroscience, The Ministry of Education and Ministry of Public Health, 38 Xueyuan Road, Beijing 100083, PR China.
Guo
Chang-Yong
CY
Yu
Peng
P
Lee
David Yue-Wei
DY
Han
Ji-Sheng
JS
Cui
Cai-Lian
CL
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000502:physiology; D005508:Food Deprivation; D005786:Gene Expression Regulation / Q000187:drug effects; D007398:Interpersonal Relations; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012054:Reinforcement, Psychology
D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D009294:Narcotics; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D009020:Morphine; C010739:ifenprodil