神经科学通报（英文版）
神經科學通報（英文版）
신경과학통보（영문판）
NEUROSCIENCE BULLETIN
2007年
1期
1-8
,共8页
刘惠芬%周文华%朱华强%赖苗军%陈为升
劉惠芬%週文華%硃華彊%賴苗軍%陳為升
류혜분%주문화%주화강%뢰묘군%진위승
海洛因%自主活动%毒蕈碱受体%FosB%伏隔核%海马
海洛因%自主活動%毒蕈堿受體%FosB%伏隔覈%海馬
해락인%자주활동%독심감수체%FosB%복격핵%해마
Heroin%locomotor activity%muscarinic receptor%FosB%nucleus accumbens%hippocampus
目的 探讨M5毒蕈碱受体亚型对海洛因诱导的大鼠行为敏化以及敏化后大脑伏隔核(NAc)和海马中FosB蛋白表达的影响.方法 建立海洛因诱导的大鼠行为敏化模型,测定大鼠的自主活动量(locomotor activity,LA),观察M5毒蕈碱受体反义寡核苷酸(M5AS-ONs)对行为敏化表达的影响.用免疫组化法测定大鼠NAc及海马齿状回(DG)FosB蛋白表达.结果 海洛因处理组与盐水处理组相比,大鼠在1小时内的LA显著增加,表明这些大鼠已稳定建立了海洛因诱导的敏化.中脑腹侧被盖区(VTA)中注射M5AS-ONs能抑制大鼠海洛因行为敏化的表达.海洛因诱导的行为敏化大鼠中NAc及DG中的FosB免疫反应阳性神经元的表达增加,而在VTA内注射M5 AS-ONs能明显抑制NAc及DG中FosB阳性神经元表达的增加;但VTA中注射有义寡核苷酸(M5S-ONs)不能明显抑制大鼠行为敏化的表达,也不能抑制海洛因敏化大鼠NAc和DG中FosB蛋白的表达.结论 阻断VTA中M5毒蕈碱受体可抑制海洛因诱导的行为敏化的表达,其机制可能和抑制大脑NAc和DG神经元中FosB蛋白的激活有关.M5毒蕈碱受体可作为改变海洛因行为学效应的有效药理学靶点之一.
目的 探討M5毒蕈堿受體亞型對海洛因誘導的大鼠行為敏化以及敏化後大腦伏隔覈(NAc)和海馬中FosB蛋白錶達的影響.方法 建立海洛因誘導的大鼠行為敏化模型,測定大鼠的自主活動量(locomotor activity,LA),觀察M5毒蕈堿受體反義寡覈苷痠(M5AS-ONs)對行為敏化錶達的影響.用免疫組化法測定大鼠NAc及海馬齒狀迴(DG)FosB蛋白錶達.結果 海洛因處理組與鹽水處理組相比,大鼠在1小時內的LA顯著增加,錶明這些大鼠已穩定建立瞭海洛因誘導的敏化.中腦腹側被蓋區(VTA)中註射M5AS-ONs能抑製大鼠海洛因行為敏化的錶達.海洛因誘導的行為敏化大鼠中NAc及DG中的FosB免疫反應暘性神經元的錶達增加,而在VTA內註射M5 AS-ONs能明顯抑製NAc及DG中FosB暘性神經元錶達的增加;但VTA中註射有義寡覈苷痠(M5S-ONs)不能明顯抑製大鼠行為敏化的錶達,也不能抑製海洛因敏化大鼠NAc和DG中FosB蛋白的錶達.結論 阻斷VTA中M5毒蕈堿受體可抑製海洛因誘導的行為敏化的錶達,其機製可能和抑製大腦NAc和DG神經元中FosB蛋白的激活有關.M5毒蕈堿受體可作為改變海洛因行為學效應的有效藥理學靶點之一.
목적 탐토M5독심감수체아형대해락인유도적대서행위민화이급민화후대뇌복격핵(NAc)화해마중FosB단백표체적영향.방법 건립해락인유도적대서행위민화모형,측정대서적자주활동량(locomotor activity,LA),관찰M5독심감수체반의과핵감산(M5AS-ONs)대행위민화표체적영향.용면역조화법측정대서NAc급해마치상회(DG)FosB단백표체.결과 해락인처리조여염수처리조상비,대서재1소시내적LA현저증가,표명저사대서이은정건립료해락인유도적민화.중뇌복측피개구(VTA)중주사M5AS-ONs능억제대서해락인행위민화적표체.해락인유도적행위민화대서중NAc급DG중적FosB면역반응양성신경원적표체증가,이재VTA내주사M5 AS-ONs능명현억제NAc급DG중FosB양성신경원표체적증가;단VTA중주사유의과핵감산(M5S-ONs)불능명현억제대서행위민화적표체,야불능억제해락인민화대서NAc화DG중FosB단백적표체.결론 조단VTA중M5독심감수체가억제해락인유도적행위민화적표체,기궤제가능화억제대뇌NAc화DG신경원중FosB단백적격활유관.M5독심감수체가작위개변해락인행위학효응적유효약이학파점지일.
Objective To investigate the effect of M5 muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it's effect on the FosB expression in the nucleus accumbens (NAc) and the hippocampus in the heroin sensitized rats. Methods Locomotor activity was measured every 10 min for 1 h after subcutaneous injection of heroin. FosB expression was assayed by immunohistochemistry, and the antisense oligonucleotides (AS-ONs) targeting M5 muscarinic receptor was transferred with the lipofectin. Results Microinjection of AS-ONs targeting M5 muscarinic receptor in the ventral tegmental area (VTA) blocked the expression of behavioral sensitization induced by heroin priming in rats. Meanwhile, the expression of FosB-positive neurons in either the NAc or the dentate gyrus (DG) of the hippocampus increased in heroin-induced locomotor sensitized rats. The enhancement of FosB-positive neurons in the NAc or DG could be inhibited by microinjection of M5 muscarinic receptor AS-ONs into the VTA before the heroin-induced locomotor sensitization was performed. In contrast, microinjection of M5 muscarinic receptor sense oligonucleotide (S-ONs) into the VTA did not block the expression of behavioral sensitization or the expression of FosB in the NAc or DG in the heroin sensitized rats. Conclusion Blocking M5 muscarinic receptor in the VTA inhibits the expression of heroin-induced locomotor sensitization, which is associated with the regulation of FosB expression in the NAc and hippocampus neurons.M5 muscarinic receptor may be a useful pharmacological target for the treatment of heroin addiction.
