Blockage of acquisition and expression of morphine-induced conditioned place preference in rats due to activation of glutamate receptors type II/III in nucleus accumbens

Numerous studies have shown that glutamate in the nucleus accumbens (NAc) is an essential neurotransmitter for the extension of morphine-induced place preference. mGlu2/3 glutamate receptors in the NAc have important roles in the reward pathway. However, less is known about the role of this glutamate receptor subtype in morphine-induced conditioned place preference (CPP). In this study, we examined the effects of bilateral intra-accumbal administration of LY379268, an mGlu2/3 receptor agonist on the acquisition and expression of morphine-induced CPP in rats. Adult male Wistar rats (n = 136; 220-250 g) were evaluated in a CPP paradigm. Doses of LY379268 (0.3, 1 and 3 μg/0.5 μL saline per side) were administered into the NAc on both sides during the 3 days of the conditioning (acquisition) or post-conditioning (expression) phase. The results show that bilateral intra-accumbal administration of LY379268 (0.3, 1 and 3 μg) markedly decreased the acquisition of morphine-induced CPP in a dose-dependent manner. In a second series of experiments, we determined that injection of LY379268 into the NAc considerably attenuated the expression of morphine CPP only at the highest dose (3 μg). Our findings suggest that activation of mGlu2/3 receptors in the NAc dose-dependently blocked both the establishment and the maintenance of morphine-induced CPP and confirmed the role of this system as a potential therapeutic target for addiction.