Adolescence is associated with an increased risk of developing drug abuse/dependence. During this ontogenetic phase, brain and hormonal systems are still undergoing crucial maturational rearrangements, which take place together with significant modifications in psychosocial development. However, the neurohormonal and behavioural facets of adolescence have been poorly investigated in relation to the vulnerability to psychostimulants such as MDMA ("ecstasy") and amphetamine. Novelty-seeking, a temperamental/behavioural trait that is typical of this age period, might substantially contribute to psychobiological vulnerability to drugs. In animal models of periadolescence, the search for novel stimuli and sensations actually shares a common neurobiological substrate (the reward-related brain mesolimbic pathways) with psychostimulants. Periadolescent mice are characterized by an unbalanced and "extremes-oriented" behaviour and by elevated levels of novelty-seeking. A deeper understanding of psychostimulant effects during adolescence, and the interaction between genetic, neurobiologic, psychosocial, and environmental factors, will lead to earlier and more effective prevention strategies.