Striatal dopamine sensitization to D-amphetamine in periadolescent but notin adult rats

The neurobiological and behavioral facets of adolescence have been poorly i nvestigated in relation to the vulnerability to psychostimulants. Periadole scent (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. Microdia lysis data indicated that AMPH-history periadolescent rats showed a promine nt sensitization of AMPH-stimulated DA release, whereas no such change was found in adult subjects. As expected, acute AMPH administration strongly re duced time spent lying still and increased levels of cage exploration in an imals 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 on ly was also characterized by a compulsive involvement in the stereotyped he ad-bobbing response. These results indicate that differently from adults, m arked alterations in neurobiological target mechanisms are observed in rats around periadolescence as a consequence of a quite mild regimen of intermi ttent AMPH exposure. Thus, a neurobiological substrate for an age-related i ncreased vulnerability towards the addictive risks of these drugs is sugges ted. (C) 2001 Elsevier Science Inc. All rights reserved.