Atypical antipsychotic medications are effective for treating both the positive and negative symptoms of schizophrenia. Olanzapine is an atypical antipsychotic that blocks dopaminergic, serotonergic, adrenergic, histaminergic, and muscarinic receptors. In this study, we used rodents to investigate whether olanzapine could suppress the hyperlocomotion, rewarding effect, and discriminative stimulus effect induced by the prototypic μ-opioid morphine, which are all considered to reflect the abuse potential or psychoactive effects of μ-opioids. Olanzapine at doses that failed to induce motor coordination produced a dose-dependent reduction in hyperlocomotion induced by morphine in mice. Olanzapine at a dose that did not produce motor dysfunction also inhibited the significant place preference induced by morphine in mice. Furthermore, the discriminative stimulus effect induced by morphine in rats was dose-dependently and significantly attenuated by olanzapine at the dose that did not induce the motor dysfunction. These results suggest that treatment with both μ-opioids and olanzapine at a dose lower than that at which it induces motor dysfunction could be very useful for preventing the abuse potential and/or psychoactive effects of μ-opioids. Synapse, 2012. © 2011 Wiley Periodicals, Inc.