Farzinpour Zahra, Taslimi Zahra, Azizbeigi Ronak, Karimi-Haghighi Saeideh, Haghparast Abbas
Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Behav Brain Res. 2019 Jan 1;356:279-287. doi: 10.1016/j.bbr.2018.08.021. Epub 2018 Sep 5.
Orexinergic system is involved in primary rewards; the neural circuit of the ventral tegmental area (VTA), nucleus accumbens (NAc), prefrontal cortex and amygdala represents overlapping elements mediating the rewarding effects of drugs and stressful experiences. The NAc integrates reward-related information from the VTA. Also, it has been indicated that orexinergic system activates the mesolimbic dopamine projecting neurons to the NAc and promotes the development of reward in rodents. Therefore, in the present study, the conditioned place preference (CPP) paradigm was used to determine the role of the two types of orexin receptors (OXR) in the NAc in forced swim stress (FSS), as physical stress, and/or priming-induced reinstatement of morphine. The CPP was induced by injecting morphine (5 mg/kg, SC for 3 days) and lasted for eight free-morphine days; the reinstatement was induced by administration of effective priming dose of morphine (1 mg/kg; sc). The extinguished rats received intra-NAc injection of SB334867 as OX1R antagonist or TCSOX229 as OX2R antagonist before effective priming dose injection of morphine (1 mg/kg; sc). In others, the extinguished rats were given intra-NAc injection of SB334867 or TCSOX229 and then, they underwent FSS before injection of ineffective priming dose of morphine (0.5 mg/kg; sc). Our results showed that intra-accumbal administration of SB334867 or TCSOX229 could inhibit morphine priming- and FSS-induced reinstatement of extinguished morphine-seeking in the rats. It seems that OXR in the NAc may be involved in reward and could play an important role in the effect of stress on reinstatement of morphine-seeking behaviors in this area.
食欲素能系统参与初级奖赏；腹侧被盖区（VTA）、伏隔核（NAc）、前额叶皮层和杏仁核的神经回路代表了介导药物奖赏效应和应激经历的重叠元素。伏隔核整合来自腹侧被盖区的奖赏相关信息。此外，有研究表明食欲素能系统激活向伏隔核投射的中脑边缘多巴胺神经元，并促进啮齿动物奖赏的形成。因此，在本研究中，采用条件性位置偏爱（CPP）范式来确定伏隔核中两种类型的食欲素受体（OXR）在强迫游泳应激（FSS）（作为身体应激）和/或吗啡引发诱导的吗啡觅药行为恢复中的作用。CPP通过注射吗啡（5mg/kg，皮下注射3天）诱导产生，并持续8天不注射吗啡；通过给予有效引发剂量的吗啡（1mg/kg；皮下注射）诱导行为恢复。在注射有效引发剂量的吗啡（1mg/kg；皮下注射）之前，对消退的大鼠进行伏隔核内注射SB334867（作为OX1R拮抗剂）或TCSOX229（作为OX2R拮抗剂）。在其他实验中，对消退的大鼠进行伏隔核内注射SB334867或TCSOX229，然后在注射无效引发剂量的吗啡（0.5mg/kg；皮下注射）之前使其接受强迫游泳应激。我们的结果表明，伏隔核内注射SB334867或TCSOX229可抑制吗啡引发和强迫游泳应激诱导的大鼠消退的吗啡觅药行为恢复。伏隔核中的食欲素受体似乎可能参与奖赏过程，并可能在该区域应激对吗啡觅药行为恢复的影响中发挥重要作用。
