A large amount of document has revealed that the orexin system in the reward circuity, including the nucleus accumbens (NAc), contributes to the modification of drug reinforcement. It has proven that the orexin receptors (OXRs) are expressed on dopamine terminals in the NAc; therefore, it can modulate reward-related behaviors. In the present study, the conditioned place preference (CPP) paradigm was used to evaluate the role of OXRs in the NAc in the acquisition and expression of methamphetamine (METH)-induced CPP. Based on previous studies, animals received METH (1 mg/kg; sc) on a 5-day schedule to induce CPP. The rats bilaterally received SB334867, OX1R antagonist, or TCS OX2 29, OX2R antagonist, (1, 10, and 30 nM/0.5 µl DMSO 12%) over five days of conditioning by METH to display the role of OXRs in reward acquisition. Moreover, the rats bilaterally received SB334867 or TCS OX2 29 in the NAc before the post-conditioning test to consider the impact of OXR antagonists on the expression of METH-induced CPP. The data revealed that the administration of SB334867 or TCS OX2 29 in the NAc led to a decrease in the acquisition of METH-induced CPP. Additionally, intra-accumbal injection of OX1R antagonist inhibited the expression of METH-induced CPP, while the OX2R antagonist failed to change this expression. Finally, the intra-NAc microinjection of both OXR antagonists was more effective in inhibiting acquisition than blocking the expression phase of METH. Data from the current study confirms that OXRs in the NAc regulate the reward-related effects of METH.

大量文献表明，奖励回路中的食欲素系统（包括伏隔核（NAc））有助于强化药物。业已证明，食欲素受体（OXRs）在NAc的多巴胺末端表达。因此，它可以调节与奖励有关的行为。在本研究中，条件位置偏爱（CPP）范式用于评估NAc中OXR在甲基苯丙胺（METH）诱导的CPP的获得和表达中的作用。根据先前的研究，动物在5天的时间内接受了METH（1 mg / kg; sc）诱导CPP。在METH调节的五天内，大鼠双边接受了SB334867（OX1R拮抗剂）或TCS OX2 29（OX2R拮抗剂）（1、10和30 nM / 0.5μlDMSO 12％），以显示OXR在奖励获取中的作用。此外，在条件调节试验之前，大鼠在NAc中双侧接受SB334867或TCS OX2 29，以考虑OXR拮抗剂对METH诱导的CPP表达的影响。数据显示，NAc中SB334867或TCS OX2 29的施用导致METH诱导的CPP的获得减少。此外，腔内注射OX1R拮抗剂抑制了METH诱导的CPP的表达，而OX2R拮抗剂未能改变该表达。最后，两种OXR拮抗剂的NAc内显微注射比阻断METH的表达阶段在抑制获取方面更有效。来自当前研究的数据证实，NAc中的OXR调节了METH的奖励相关效应。