Aims: Previous investigations demonstrated that tramadol, as a painkiller, similar to morphine induces tolerance and dependence. Furthermore, the cannabinoid receptor 1 (CB1R) located in the nucleus accumbens (NAc) plays a critical role in morphine-induced conditioning. Therefore, the main objective of this study was to evaluate the role of NAc CB1R in tramadol induced conditioning and reinstatement.

Main methods: In the present experiment, the effect of NAc CB1 receptors on tramadol induced conditioning was tested by microinjecting of arachidonylcyclopropylamide (ACPA, CB1R agonist) and AM 251 (CB1R inverse agonist) in the NAc during tramadol-induced conditioning in the adult male Wistar rats. In addition, the role of NAc CB1R in the reinstatement was also evaluated by injecting ACPA and AM 251 after a 10-days extinction period.

Key findings: The obtained data revealed that the administration of tramadol (1,2, and 4 mg/kg, ip) dose-dependently produced conditioned place preference (CPP). Moreover, intra-NAc administration of ACPA (0.25, 0.5, and 1 μg/rat) dose-dependently induced conditioning, while the administration of AM-251 (30, 60, and 120 ng/rat) induced a significant aversion. In addition, the administration of a non-effective dose of AM251 during tramadol conditioning inhibited conditioning induced by tramadol. On the other hand, the administration of ACPA after extinction induced a significant reinstatement. Notably, the locomotor activity did not change among groups.

Significance: Previous studies have shown that tramadol-induced CPP occurs through μ-opioid receptors. The data obtained in the current study indicated that CB1R located in the NAc is involved in mediating conditioning induced by tramadol. Besides, CB1R also plays a vital role in the reinstatement of tramadol-conditioned animals. It might be due to the effect of opioids on enhancing the level of CB1R.

目的：先前的研究表明曲马多作为一种止痛药，与吗啡相似，可诱导耐受性和依赖性。此外，位于伏伏核（NAc）中的大麻素受体1（CB1R）在吗啡诱导的调节中起关键作用。因此，本研究的主要目的是评估NAc CB1R在曲马多引起的调节和恢复中的作用。

主要方法：在本实验中，通过在成年男性曲马多诱导的调理过程中向NAc中微量注射花生四烯酸环丙基酰胺（ACPA，CB1R激动剂）和AM 251（CB1R反向激动剂）来测试NAc CB1受体对曲马多诱发的调节作用Wistar大鼠。此外，还通过在灭绝10天后注射ACPA和AM 251来评估NAc CB1R在修复中的作用。

关键发现：获得的数据表明，曲马多（1,2，和4 mg / kg，ip）的剂量依赖性产生条件性位置偏爱（CPP）。此外，NAc内ACPA（0.25、0.5和1μg/只）的剂量依赖性诱导条件调节，而AM-251（30、60和120 ng /只）的诱导剂量则引起明显的反感。另外，在曲马多调理过程中施用非有效剂量的AM251抑制了由曲马多引起的调理。另一方面，灭绝后施用ACPA引起明显的恢复。值得注意的是，运动活性在各组之间没有改变。

意义：先前的研究表明，曲马多诱导的CPP通过μ阿片受体发生。在当前研究中获得的数据表明，位于NAc中的CB1R参与了由曲马多诱导的调解。此外，CB1R在恢复曲马多条件下的动物中也起着至关重要的作用。这可能是由于阿片类药物对提高CB1R水平的作用。