Background: Morphine is one of the most effective analgesics used to treat postoperative or cancer pain. A major drawback of its continuous use is the development of tolerance and dependence. U-50488, a selective κ-opioid receptor agonist has been reported to suppress the development of antinociceptive tolerance to morphine in animals. Here we further investigated its effect on morphine addiction. Methods: Conditioned place preference (CPP) test and behavioral sensitization of locomotor activity were used to investigate drug-seeking related behaviors associated with psychological dependence in Sprague Dawley rats. Microdialysis and high-performance liquid chromatography were used to determine the extracellular level of dopamine metabolites in the shell region of the nucleus accumbens (NAc). Results: Coadministered U-50488 was able to abolish both the CPP effect and behavioral sensitization induced by morphine. A significant increase of dopamine metabolites following morphine administration was demonstrated in the NAc. This increase by morphine could be attenuated by coadministered U-50488, whereas U-50488 itself did not show significant effects. Conclusions: U-50488 might effectively attenuate morphine-induced psychological dependence. Neurochemical analysis suggested that U-50488 could be acting by inhibiting the dopaminergic mesolimbic pathway activated by morphine, which is believed to cause rewarding.