Effects of repeated intracerebroventricular microinjections of 18 nmol/10 microl of neurotensin, [D-Tyr11]neurotensin, or saline were tested on motor activity in different groups of rats. One week after the fourth central injection, sensitivity to the behavioral stimulant effect of amphetamine (1 mg/kg, i.p.) was tested. As previously reported, neurotensin attenuated motor activity while [D-Tyr11]neurotensin when compared to saline produced an initial suppression followed by an excitation. Despite such different behavioral effects, both peptides produced sensitization to the stimulant effect of amphetamine. These results show that repeated activation of neurotensin receptors produces long-lasting changes in responsiveness to a psychostimulant drug.