Repeated morphine treatments result in sensitization, an increase in the efficacy of morphine to stimulate locomotor activity. study examined the effects of increasing serotonin (5-hydroxytryptamine, 5-HT) transmission on morphine-sensitization. For five days rats were administered saline or 5.0 mg/kg fluoxetine prior to treatment with saline or 5.0 mg/kg morphine. Twenty-one days later, rats were tested for their locomotor response to 2.0 mg/kg morphine. Fluoxetine treatment attenuated the locomotor activating effect of acute morphine treatments and blocked the sensitized response to the morphine challenge. These results indicate that increased 5-HT transmission attenuates the locomotor stimulating effects of morphine and prevents the development of morphine-sensitization.