摘要
通过慢性吗啡处理方式建立起SD大鼠吗啡依赖的条件化位置偏好(CPP)模型,用行为学手段研究多巴胺(DA)D2受体拮抗剂及激动剂对SD大鼠CPP的影响,探讨眶额叶DAD2受体在阿片精神依赖中的作用。通过腹腔注射吗啡同环境因素相结合,建立大鼠吗啡依赖的CPP模型;采用局部脑内微量注射法向额叶注射DAD2受体拮抗剂或激动剂或盐水(对照组),以得到SD大鼠在戒断期间的CPP的时间数据。CPP显示DAD2受体拮抗剂组与对照组相比,从戒断第2天起,前者表现出更明显的CPP增加现象,差异显著(P<0·05)。而DAD2受体激动剂组与对照组相比无显著差异(P>0·05)。采用腹腔小剂量注射吗啡,成功地建立了吗啡依赖SD大鼠的CPP模型;眶额叶微量注射DAD2受体拮抗剂增加了CPP时间,提示眶额叶多巴胺系统在吗啡依赖的过程中有着较为重要的作用;也提示了对于已经成瘾的动物,损伤其眶额叶,会使药物渴求增强。因而提示对于药物依赖患者进行手术干预治疗要极其慎重。
With conditional place preference (CPP) of morphine dependent rats, the study focus on the effects of the DAD2 receptor in the orbital frontal cortex (OFC) in rat associated with the processing of opioid dependence. CPP models of morphine dependent rats were established by intraperintoneal injection and combined with environmental stimulation. Rats were derided into three groups received Quinpirole or Raclopride injection (agonist or antagonist of the DAD2 receptor) in OFC by a minim-injector after the last conditioning session and CPP was assessed by the time spent in the morphine-associated environment after conditioning. All dates were analysed by statistical method. The time in drug place of Raclopride intervene group showed respectively significantly longer than the control group in the 2nd withdrawal day (P 〈 0.05), however the time of Quinpirole intervene group didn't show significant difference compared with control group (P 〉 0.05). The results indicated that: (1) CPP models of morphine dependent rats were established successfully by intraperintoneal injection with the proper dosage with the reference of many related papers; (2) The DA system in OFC plays an important role in the procession of morphine dependence; (3) The damnification in orbital frontal cortex of animals who addicted in drugs will increase their drugs craving behavior. Clinically, it might indicate that we must cautiously operate intervention to the patients of drug addiction.
关键词
吗啡
条件化位置偏好
药物依赖
眶额叶
渴求
多巴胺
Morphine
Conditional place preference
Drug dependence/addiction
Orbital frontal cortex
Craving
Dopamine