Effect of intrathecal NR2B antisense oligonucleotide on congnitive function in morphine-dependent rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of intrathecal (IT) NR2B antisense oligonucleotide (aNR2B) on cognitive function in morphine-dependent rats.Methods Male SD rats weighing 230-270 g were used in this study. The animals were anesthetized with intraperitoneal pentobarbital 60 mg/kg.IT catheter was placed at L3-4 interspace according to the technique described by Yang. Thirty rats in which IT catheter was successfully placed without any complication were randomly divided into 3 groups(n=10 each)control group (group C), morphine dependence group (group MD) and group aNR2B.Morphine dependence was induced in group MD and aNR2B by increasing doses of morphine for 6 days. The initial dose of morphine was 10mg/kg injected subcutaneously (SC) twice a day and was increased by 10 mg/kg.every other day.The final dose was 50mg/kg. Then morphine 30 mg/kg was administered SC once a day for 4 weeks. aNR2B 15 nmol was administered IT at 30 min before SC morphine every day in group aNR2B.In control group normal saline was administered instead of morphine. Morris water maze was used to assess the cognitive function at 0 (T0, baseline),1 and 3 weeks of morphine administration (T1,T2).The escape latency and the number of times the animals crossing the plateform were recorded. The animals were killed after the test and the hippocampus was isolated for determination of choline acetytransferase(ChAT)expression.Results There was no significant difference in the baseline escape latency and the baseline number of times the animals crossing the plateform at T0 among the 3 groups. The escape latency was significantly prolonged and the number of times the animals crossing the plateform decreased at T1 and T2 as compared with the baseline at T0 in group MD.The ChAT expression was significantly down-regulated in group MD as compared with control group. IT aNR2B significantly ameliorated cognitive dysfunction at T1 and T2 and increased ChAT expression in group aNR2B compared with group MD.Conclusion IT NR2B antisense oligonucleotide can attenuate cognitive dysfunction through up-regulation of ChAT expression in hippocampus in morphine-dependent rats.