Effect of NR2B antisense oligonucleotide on naloxone-induced withdrawal responses in morphine-dependent rats
10.3760/cma.j.issn.0254-1416.2010.03.025
- VernacularTitle:鞘内注射NR2B反义寡核苷酸对纳洛酮诱发吗啡依赖大鼠戒断反应的影响
- Author:
Yi WEI
;
Yisa SHI
;
Shuangyin ZHANG
;
Yongfeng MA
- Publication Type:Journal Article
- Keywords:
Receptors,N-methyl-D-aspartate;
Oligonucleotides,antisense;
Injections,spinal;
Morphine dependence;
Naloxone;
Substance withdrawal syndrome
- From:
Chinese Journal of Anesthesiology
2010;30(3):334-336
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of NR2B antisense oligonucleotide on naloxone-induced withdrawal responses in morphine-dependent rats. Methods Famale SD rats weighing 230-270 g were anesthetized with intraperitoneal pentobarhital 60 mg/kg. Intrathecal (IT)catheter was placed at L3,4 interspace.Thirty-two rats in which FT catheter was successfully placed were randomly divided into 4 groups ( n = 8 each) : group C control; group MD morphine dependence; group AO NR2B antisense oligonucleotide (aNR2B) and group SO NR2B sense oligonucleotide (sNR2B) . In group MD, AO, SO chronic morphine dependence was induced by increasing doses of subcutaneous morphine for 6 days. The initial dose of morphine was 10 mg/kg twice a day and was increased by 10 mg/kg twice every other day and reached 50 mg/kg on the 6th day. In group AO and SO IT aNR2B or sNR2B 15 nmol was administered simultaneously with subcutaneous morphine. Morphine withdrawal responses was induced by IT naloxone 4 mg/kg and scored based on the responses (0 = normal; higher scores signify severer responses) . The weight loss was calculated.The expression of NR1, NR2A and NR2B mRNA in hippocampus was determined by RT-PCR. Results The morphine withdrawal syndrome and weight loss were significantly incresed in group MD, AO and SO, while NR2B mRNA expression in hippocampus was up-regulated in group MD and SO compared with group C. The morphine withdrawal syndrome and weight loss were significantly decreased, NR2A mRNA expression in hippocampus was up-regulated and NR2B mRNA expression was down-regulated in group AO compared with group MD. There was no significant difference in NR1 mRNA expression between the 4 groups . Conclusion NR2B antisense oligonucleotide can suppress morphine withdrawal responses through the regulation of NMDA receptor level and construction in hippocampus.
