中脑腹侧被盖区和伏隔核内食欲素Ⅰ型受体在大鼠觅药行为表达中的作用

The Roles of OrexinⅠReceptor in Ventral Tegmental Area and Nucleus Accumbens in Drug-seeking Behavior Induced by Morphine

目的:探讨中脑腹侧被盖区(VTA)和伏隔核(NAc)内食欲素Ⅰ型受体在大鼠觅药行为表达中的作用。方法:以吗啡条件性位置偏爱(CPP)表达作为大鼠觅药行为模型,88只雄性Wistar大鼠随机进入VTA干预组和NAc干预组,偏爱测试前分别在VTA和NAc内注射食欲素Ⅰ型受体(OXR1)拮抗剂SB334867(VTA:1,5μg;NAc:1,3μg)或溶剂(DMSO),考察其对CPP表达的影响。采用单因素方差分析比较了各组间的偏爱值。结果:吗啡CPP表达前VTA注射5μgSB334867组动物的偏爱值(73.6±81.7)低于溶剂处理组(183.5±30.4);吗啡CPP表达前NAc注射SB334867组动物的偏爱值(229.6±72.9和260.6±53.9)与溶剂处理组(224±52.1)之间无显著差异。结论:食欲素通过激活VTA内食欲素Ⅰ型受体促进药物相关环境线索诱发的大鼠觅药行为表达,而NAc内的食欲素Ⅰ型受体不参与觅药行为表达。本研究为揭示食欲素参与觅药行为表达的神经机制提供了线索。

Objective： To investigate the roles of OXR1 in the ventral tegmental area （VTA） and nucleus accumbens （ NAc） in drug-seeking behavior induced by morphine. Methods： Drug-seeking behavior in rats was measured with the model of expression of morphine conditioned place preference （ CPP ）. Eighty-eight male Wistar rats were randomly incorporated into the VTA-treated groups and NAc-treated groups. The OXR1 selective antagonist SB334867 （VTA： 1, 5μg; NAc： 1, 3μg） or vehicle （Dmethyl Sulfoxide） were microinjected into the VTA and NAc respectively before CPP expression tests. The one-way ANOVA was used to compare the preference scores among groups. Results： The preference score was significantly reduced in animals microinjected with 5μg SB334867 compared with that in animals microinjected with vehicle into the VTA before CPP expression test [ （73.6 ± 81.7） vs. （ 183.5 ±30. 4） , P 〈 0. 05 ] ; There was no significant difference between the preference score in animals microinjected with SB334867 （229. 6 ±72. 9 and 260. 6 ± 53.9） and that in animals mieroinjected with vehicle （224 ±52.1 ） into the NAe before CPP expression test. Conclusion： The activation of OXR1 in the VTA plays an important role in drug-seeking behavior elicited by morphine-associated environmental cues, while OXR1 in the NAc is not involved in this behavior. The present study suggests some neural mechanisms underlying the roles of orexins in drug-seeking behavior.