Uridine interacted with the dopaminergic system and regulated dopamine-related behaviors in role of potential endogenous neuromodulator of the GABAA receptor.The present study investigated the effects of uridine on morphine-induced hyperactivity and on modulating dopaminergic neurotransmission in mice, which may help to understand how uridine acts as modulators of the GABAA receptor.The results showed that uridine (30 or 100 mg· kg-1) significantly attenuated the hyperactivity induced by acute morphine treatment in mice.Morever uridine could increase the extracellular levels of GABA in the brain.In addition, the GABAAreceptor antagonist, significantly attenuated the effect of uridine on morphineinduced hyperactivity.In vivo microdialysis demonstrated that uridine reversed morphine-induced dopamine release in the dorsal striatum of morphine-treatment mice.In conclusion, these data suggested that the therapeutic effect of uridine on morphine-induced hyperactivity may be mediated in part by interfering with the dopaminergic system possibly via agonistic effects at GABAA receptors.