地卓西平对吗啡依赖大鼠部分脑区突触素ⅠmRNA表达的影响

Effect of dizocilpine on synapsinⅠmRNA expression in defined brain regions of morphine dependent rats

目的:研究地卓西平对吗啡依赖大鼠部分脑区突触素ⅠmRNA表达的影响。方法:雄性SD大鼠24只,随机等分为2组。吗啡组大鼠腹腔注射盐酸吗啡,2次/d,起始剂量5mg/kg,逐d递增5mg/kg,至第10d达50mg/kg;干预组大鼠在每次注射吗啡(同吗啡组)前30min腹腔注射地卓西平0.075mg/kg。末次注射后3h及72h,2组各取6只大鼠取脑并冰冻切片,留取中脑腹侧被盖区(VTA)、伏隔核(NAc)、中脑导水管灰质(PAG)、杏仁核(AMG)、海马CA1区(HIPCA1)的脑片,利用原位杂交技术检测突触素ⅠmRNA的表达。结果:末次注射后3h,干预组大鼠AMG、HIPCA1突触素ⅠmRNA的表达高于吗啡组;72h时,干预组大鼠NAc、HIPCA1突触素ⅠmRNA的表达高于吗啡组(P均<0.05)。其他脑区2组间差异无统计学意义(P>0.05)。结论:地卓西平可促进吗啡依赖大鼠部分脑区突触素Ⅰ基因的表达,这可能是其抑制吗啡依赖效应的机制之一。

Aim： To explore the effect of dizocilpine on synapsin I gene expression in defined brain regions of morphine dependent rats, Methods： Twenty-four male SD rats were randomly and equally allocated into morphine group and intervention group. Rats in morphine group were abdominally injected morphine from a dose of by 5 mg/kg and increased by 5 mg/kg per day till increased to 50 mg/kg at the 10th day,twice per day. Rats in intervention group were treated as the morphine group and given dizocilpinc 0. 075 mg/kg at 30 min before morphire injection. At 3 h and 7 h after the last injection, the rat brain tissue was removed,and the synapsin I mRNA levels in ventral tegmental area （VTA） , nucleus accumbens （NAc） , periaqueductal gray （PAG）, amygdala （AMG） , hippocampus CA1 （HIPCA1） were determined by in situ hybridization. Results： The synapsin I mRNA levels of intervention group in AMG and HIPCA1 at the time-point of 3 h, and in NAc and HIPCA1 at the time-point of 72 h were significantly higher than those of morphine group. Conclusion： Dizocilpine may enhance the gene expression of synapsin I in defined brain regions of morphine dependent rats, which might be one of the mechanisms of dizocilpine attenuating morphine dependence.