摘要
目的检测吗啡条件性位置偏爱重现大鼠下丘脑和血浆中神经甾体含量的变化。方法建立大鼠对吗啡的条件性位置偏爱(conditionedplacepreference,CPP),CPP消退后用足底电击(footshock)诱发CPP的重现。将大鼠断头取血并取出下丘脑,制备组织匀浆,采用液-液萃取和固相萃取法提取下丘脑和血浆中的神经甾体,经衍生化后,采用高效液相色谱-质谱法测定神经甾体含量。结果与生理氯化钠溶液对照组相比,吗啡CPP重现组大鼠下丘脑中的PREG和PREGS的水平分别升高36%和60%(P<0.05)。与CPP消退组相比,吗啡CPP重现组大鼠下丘脑中的PREGS水平升高60%(P<0.05);吗啡CPP重现组大鼠血浆中的DHEAS水平下降33%(P<0.01)。结论足底电击应激诱发吗啡CPP重现时,大鼠下丘脑中的神经甾体PREG、PREGS和DHEAS水平不依赖于血浆中相应的甾体水平变化,其中枢作用可能与应激诱发的吗啡CPP重现行为有关。下丘脑中的PREG和PREGS可能通过其对GABA系统的作用参与足底电击应激诱发的大鼠吗啡CPP重现。
Aim To investigate the effect of reinstatement to morphine conditioned place preference （CPP） on neurosteroids levels in rat hypothalamus and plasma. Methods A CPP rat model was established with morphine injection. Mterextinction, footshock was used to induce the reinstatement. Then the rats were decapitated, tnmk blood was collected andhypothalamus was dissected out. After homogenation, liquid-liquid extraction and solid phase extraction were used to extract the neurosteroids from hypothalamus and plasma. The extracted fractions were then derivatized and quantitated byHPLC-MS. Results Compared with saline control group, pregnenolone （PREG） and pregnenolone sulfate （PREGS） levelsin rat hypothalamus in the reinstatement group increased by 36% and 60% respectively （ P 〈 0.05）. Compared withCPP extinct group, the PREGS level in rat hypothalamus increased by 60% （ P 〈 0.05） ;dehydroepiandrosterone sulfate（DHEAS） level in rat plasma decreased by 33% （ P 〈 0.01 ） in the morphine CPP reinstated group. ConclusionChanges of PREG, PREGS and DHEAS levels in hypothalamus are independent of those in plasma when reinstatement tomorphine CPP was induced by footshock. The effect of these neurosteroids in the central nervous system may play a role instress induced reinstatement to morphine CPP. Levels of PREG and PREGS in rat hypothalamus may participate in thefootshock induced reinstatement to morphine CPP through their effect on gamma-aminobutyric acid （GABA） system.
出处
《解放军药学学报》
CAS
2006年第2期84-87,共4页
Pharmaceutical Journal of Chinese People's Liberation Army
基金
河北省自然科学基金资助项目
No.C2005000834
关键词
吗啡
条件性位置偏爱
足底电击
下丘脑
神经甾体
Morphine
Conditioned place preference
Footshock
Hypothalamus
Neurosteroids
