大鼠海马CA2区GDNF mRNA表达与吗啡依赖和吗啡的关系

Involvement of Hippocampus in the Development of Morphine-withdrawal Rats

【目的】观察吗啡戒断大鼠侧脑室胶质细胞源性神经营养因子(GDNF)反义寡脱氧核苷酸注射后对海马GDNF mRNA表达的影响。【方法】SD大鼠侧脑室立体定位,皮下注射吗啡建立吗啡依赖大鼠模型,侧脑室微注射GDNF有义和反义寡脱氧核苷酸,纳洛酮催促戒断,应用原位杂交方法检测海马GDNF mRNA的表达。【结果】侧脑室注射GDNF反义寡脱氧核苷酸能显著抑制大鼠吗啡戒断症状评分(P<0.05)。吗啡依赖大鼠海马CA2区GDNF mRNA表达较对照组显著增加(P<0.05),CA1和CA3区变化不明显;吗啡依赖大鼠纳洛酮(4mg/kg,ip)催促戒断后海马CA1、CA2和CA3区GDNF mRNA表达较依赖组有增加趋势,但均没有显著差异(P>0.05);吗啡依赖大鼠纳洛酮激发前24h侧脑室注射GDNF反义寡脱氧核苷酸能显著抑制吗啡依赖大鼠依赖和戒断后CA2区GDNF mRNA表达的增加(P<0.05),而CA1和CA3区与戒断组大鼠相应区域相比没有差异;吗啡依赖大鼠纳洛酮激发前24h侧脑室注射GDNF有义寡脱氧核苷酸与戒断组大鼠相比海马CA1、CA2和CA3区GDNF mRNA表达均没有显著性差异(P>0.05)。【结论】在转录水平,海马CA2区GDNF表达的变化在吗啡依赖和戒断中可能起重要作用。

[Objective]To observe glial cell-derived neurotrophic factor （GDNF） mRNA expression in hippocampus of morphine- withdrawal rats after microinjecting GDNF antisense oligonucleotide into lateral ventricle, [Methods]SD rats were used to establish morphine dependence model in rats. GDNF antisense and sense oligonucleotides were microinjected into rat lateral ventricle, then GDNF mRNA expression of hippocampus was detected by in situ hybridization. [Results]Injection of GDNF antisense oligonucleotides into lateral ventricle decreased the scores of morphine-withdrawal syndrome. The expression of GDNF mRNA in hippocampus CA2 zone increased in morphine- dependent and withdrawal rats. The up- regulated expression of GDNF mRNA in hippocampus CA2 zone could be inhibited by microinjection of GDNF antisense oligonucleotide into lateral ventricle. In contrast, microinjection of GDNF sense oligonucleotide did not block the expression of GDNF mRNA in hippocampus CA2 zone of morphine-withdrawal rats. [Conclusion]The results suggest that the expression of GDNF mRNA in hippocampus CA2 zone plays an important role in morphine-dependence and.withdrawal on transcription level.