【摘要】 目的　研究不同毒蕈碱受体亚型 (M4,M5)对吗啡诱发大鼠奖赏效应的影响 ,同时观察腹侧背盖区 (ventraltegmentalarea ,VTA)神经型一氧化氮合酶 (nNOS)表达的变化。方法　实验通过侧脑室置管给药 ,采用反义寡核苷酸技术 ,免疫组织化学技术和条件位置偏爱 (conditionedplacepreference,CPP)程序 ,研究M4,M5反义寡脱氧核苷酸干预下吗啡的奖赏行为 ,以及VTA内nNOS表达情况。结果　吗啡 (5mg·kg-1)皮下注射 ,可以建立起稳定的大鼠对伴吗啡环境的位置偏爱 ,同时VTA内nNOS阳性神经元表达也显著增加。而M5反义寡脱氧核苷酸 (M5 AS) (2nmol)侧脑室预注射则可阻断吗啡诱发CPP的形成 ,同时也显著减少VTA内nNOS表达。在吗啡诱发的CPP形成后 ,侧脑室单次注射M5 AS(2nmol)也可以逆转大鼠对伴吗啡环境的位置偏爱 ,同时也明显减少VTA内nNOS表达。相比之下 ,M4反义寡脱氧核苷酸 (M4 AS)对吗啡诱发的CPP形成以及VTA内nNOS表达的影响均不明显。实验前后所有大鼠的运动活性并未发生显著改变 ,可排除运动活性对实验的影响。结论　M5毒蕈碱受体在大鼠吗啡诱发的条件位置偏爱形成过程中起重要作用 ;M5毒蕈碱受体可能是通过激活大鼠VTA内nNOS的表达 ,参与调控吗啡奖赏效应的。更多还原

【Abstract】 Aim To investigate the roles of different muscarinic receptors (M 4, M 5) subtype on rewarding effects induced by morphine and the changes of neuronal nitric oxide synthase(nNOS)expression in ventral tegmental area (VTA) of rats. Methods Antisense oligonucleotides (AS-ONs) technique, lateral ventricle injection, and nNOS immunohistochemistry were employed in the present study, conditioned place preference (CPP) model was used for evaluating the rewarding effects of morphine in rats.Results After rats were injected morphine (5 mg·kg -1, sc), the time that rats stayed in paired-morphine boxes was significantly lengthened, and the amount that nNOS positive neurons expressed in VTA obviously increased. 24 h before injection of morphine, pretreatment with M 5-antisense oligodeoxynucleotides (M 5-AS) (2 nmol, icv) significantly inhibited formation of CPP and activation of nNOS expression in VTA. After the morphine-induced CPP had been established, injection of M 5-AS (2 nmol, icv) reduced the time that rats stayed in paired-morphine boxes, and in VTA the amount of nNOS positive neurons also reduced. In contrast with M 5-AS, M 4-antisense oligodeoxynucleotides (M 4-AS) had no great effects on the morphine-induce CPP and the expression of nNOS positive neurons in VTA. In addition, locomotor activity in all rats had no obvious changes in study.Conclusions M 5 muscarinic receptor play an important role in the conditioned place preference induced by morphine; M 5 muscarinic receptor activate expression of nNOS positive neurons in VTA, which maybe involved in morphine reward.更多还原