伏隔核和中脑腹侧被盖区内食欲素在吗啡奖赏中的作用

实验采用条件性位置偏爱（CPP）模型考察中脑腹侧被盖区（VTA）和伏隔核壳区（NAcSh）内食欲素（orexin）在吗啡奖赏中的作用。Wistar大鼠分为盐水训练组和吗啡训练组。3轮吗啡（或盐水）匹配训练前，双侧VTA或NAcSh内给予OXR1拮抗剂SB334867（VTA: 0, 1, 5μg；NAcSh: 0, 1, 3μg）；或2轮吗啡（或盐水）匹配训练前NAcSh内给予orexin A（0, 2, 4, 6μg），观察其对吗啡CPP建立的影响。结果表明，VTA内给予SB334867抑制吗啡CPP建立，并存在剂量效应关系；NAcSh内给予SB334867或orexin A均未影响吗啡CPP建立，而orexin A可增加吗啡处理大鼠的运动性。以上结果表明，VTA和NAcSh内的orexin在吗啡奖赏中扮演的角色不同，可能调控成瘾行为的不同成分

The Roles of Orexins in the Nucleus Accumbens and Ventral Tegmental Area on Reward-Associated Behavior Induced by Morphine

Orexins are neuropeptides produced by the hypothalamus. Orexin neurons have extensive projections to the mesolimbic dopamine system (MLSD) and are critically involved in drug addiction. The central nucleus of the MLSD, the ventral tegmental area (VTA) and nucleus accumbens (NAc), contain abundant orexinergic fibers and receptors. In the VTA, orexins are implicated in drug reward-elicited place preference and acquisition of behavioral sensitization. However, less study has been focused on the role of orexins in the NAc in drug reward by now. The present study aims to investigate the roles of orexins in the VTA and NAc in drug reward-associated behavior. The development of conditioned place preference (CPP) induced by morphine was used to investigate the roles of orexins in the VTA and NAc in drug reward. The apparatus for the CPP was consisted of two distinctive compartments. The 135 male Wistar rats were alternatively treated with morphine (3mg/kg) or saline before conditioning training (45min), with one injection per day. Before three conditioning sessions with morphine, the OXR1 antagonist SB334867 was bilaterally microinjected into the VTA (0, 1, 5 μg) or NAcSh (0, 1, 3 μg). Before two conditioning sessions with morphine, orexin A (0, 2, 4, 6 μg) was bilaterally microinjected into the NAcSh. One-way ANOVA and Post Hoc LSD were used to reveal the difference among groups. The results showed that the development of morphine CPP was inhibited when SB334867 was infused into the VTA and not affected when SB334867 was infused into the NAcSh. Orexin A microinjected into the NAcSh did not enhance or inhibit morphine CPP, but increased locomotor activity especially in the rats treated with morphine. The present study demonstrated the different roles of orexins in the VTA and NAcSh in drug reward induced by morphine, indicating that orexins in these two brain regions might regulate the different aspects of addictive behavior.