鞘内注射NR2B反义寡核苷酸对吗啡戒断大鼠海马NMDA受体亚基mRNA表达的影响

Objective To investigate the influence of NR2B antisense oligonucleotide on the mRNA expression of N-methyl-D-aspartate receptor (NMDAR) subunits in the rat hippocampus and how this relates to morphine dependence. Methods Thirty-two adult female Sprague-Dawley rats weighing 230～270g were randomly divided into 4 group(n=8 each):A control;B morphine dependence;C NR2B antisense oligonucleotide (ANR2B);D NR2B sense oligonucleotide (SNR2B). A model of chronic morphine dependence was established by repeated subcutaneous injection of morphine with progressive doses. Additionally, rats were treated with intrathecal (i.t.) injection of either saline, ANR2B or SNR2B. Morphine dependence was characterized by the total score of naloxone-precipitated withdrawal and weight loss .The method of reverse transcription polymerase chain reaction (RT-PCR) was used to study the expression of NR1，NR2A and NR2B mRNA in rat hippocampus. Results The total score of morphine-withdrawal symptoms and the number of weight loss were higher in group B or D than in group C (P<0.01). Increase in NR2B mRNA expression in the hippocampus induced by morphine were significantly attenuated by ANR2B.Conclusion These results indicate that morphine dependence is related to the regulation of NMDA receptor，s level and construction in the hippocampus.