Research articleRole of intra-accumbal orexin receptors in the acquisition of morphine-induced conditioned place preference in the rats

•Bilateral intra-NAc injection of SB334867 attenuated the acquisition of morphine-induced CPP.•Blockade of OX2 receptors in the NAc decreased the acquisition of morphine-induced CPP.•Contribution of OX1 receptors to the development of morphine-induced CPP was more than NAc OX2 receptors.

Orexin receptor shave essential role in the induction of reward-related behaviors to several drugs of abuse. In the present study, we investigated the effects of bilateral administration of SB334867, as an orexin-1 receptor antagonist, and TCS OX2 29, as an orexin-2 receptor antagonist, into the nucleus accumbens (NAc) on the acquisition of morphine-induced conditioned place preference (CPP) in the rats. Adult male Wistar rats (n = 80; 220-250 g) were entered in a CPP paradigm. Bilateral microinjections of different doses of SB334867 (1, 3, 10 and 30 nM) or TCS OX2 29 (3, 10, 30 and 100 nM) into the NAc (0.5 μl/side) were done 5 min before subcutaneous injection of morphine (5 mg/kg) during 3-dayconditioning (acquisition) phase. The CPP scores and locomotor activity of animals were recorded by video tracking system and Ethovision software. The results demonstrated that intra-NAc microinjection of 3, 10 and 30 nM solutions of SB334867 markedly decreased the acquisition of morphine-induced CPP in a dose-dependent manner. Intra-accumbal injection of 10, 30 and 100 nM solutions of TCS OX2 29 significantly attenuated the acquisition of morphine CPP as well. In addition, contribution of orexin-1 receptors to development of morphine reward-related behaviors was more than orexin-2 receptors. Our results suggest that both orexin-1 and −2 receptors in the NAc are involved in the development of morphine-induced CPP. It seems that orexin-1 receptors in this region are more effective in development of drug seeking behaviors in the rats.