吗啡依赖大鼠部分脑区前脑啡肽基因表达改变

Decreased expression of proenkephalin mRNA in defined regions of morphine dependent rats

目的 研究吗啡依赖大鼠部分脑区的前脑啡肽基因(PENK)转录水平的改变。方法 将24只雄性Sprague-Dawlay大鼠随机等分为吗啡组(iq·2次·d-1,剂量逐日递增,5-50mg·kg·次,共10d)及对照组(注射相同体积的生理盐水)。在末次注射后的3h及3d,每组各随机灌注处死6只,取脑组织并冰冻切片,留取含中脑腹侧被盖区(VTA)、伏隔核(NAC)、中脑导水管灰质(PAG)、杏仁核(AMG)、海马CAl区(HIPCAl)的切片。利用原位杂交技术及图像分析技术检测各脑区吸光度A值(PENKmRNA)的水平。结果末次注射后3h,吗啡组大鼠5个被检脑区PENK mRNA值,均显著低于同期对照组;末次注射后3d,在除AMG以外的4个被检脑区PENK mRNA值仍显著低于同期对照组。结论慢性吗啡处理可使多个脑区PENK基因表达明显下调,从而参与吗啡依赖与戒断。

Objective To investigate gene expression of proenkephalin mRNA in defined regions of morphine dependent rats. Methods Twenty - four male Sprague - Dawlay rats were randomly assigned to morphine group (injected intraperi-toneally with morphine b.i.d. for 10 days in ascending dosage schedule) and control group (injected intraperitoneally with saline) . Upon 3h and 3d following the last injection, 6 rats per group were perfused and brains were removed and cut coronally. The sections containing ventral tegmental area (VTA), nucleus accumben (NAc), periaqueductal gray (PAG), amygdala (AMG), hippocampus CA1(HIPCA1) were selected and mounted on slides. The mRNA levels of PENK were assayed by in situ hybridization. Results Compareing with the PENK mRNA levels in control rats of the two time - pionts respectively, the PENK mRNA levels decreased significandy in all detected areas at the timepoint of 3h and in VTA, NAc, PAG, HIPCA1, but not in AMG, at the timepoint of 3d in morphine- treated rats. Conclusion Chronic morphine administration may down - regulate the expression of PENK, which contributes to the development of morphine dependence and abstinence syndrome.