The neurobiological and behavioral facets of adolescence have been poorly investigated in relation to the vulnerability to psychostimulants. Periadolescent (33-43 days) and adult (>70 days) Sprague-Dawley rats underwent a 3-day treatment history with D-amphetamine (AMPH) at 0, 2, or 10 mg/kg (once a day). After a short 5-day-long withdrawal interval, freely moving animals were challenged with a 2-mg/kg AMPH dose and their behavior as well as in vivo intrastriatum dopamine (DA) release in the CNS were assessed. Microdialysis data indicated that AMPH-history periadolescent rats showed a prominent sensitization of AMPH-stimulated DA release, whereas no such change was found in adult subjects. As expected, acute AMPH administration strongly reduced time spent lying still and increased levels of cage exploration in animals of both ages. A treatment history of high AMPH dosage was associated with a marked sensitization of the exploratory behavior in adults, whereas it induced a quite opposite profile in periadolescents. The latter group only was also characterized by a compulsive involvement in the stereotyped head-bobbing response. These results indicate that differently from adults, marked alterations in neurobiological target mechanisms are observed in rats around periadolescence as a consequence of a quite mild regimen of intermittent AMPH exposure. Thus, a neurobiological substrate for an age-related increased vulnerability towards the addictive risks of these drugs is suggested.