Psychobiological risk factors for vulnerability to psychostimulants in human adolescents and animal models

Adolescence is associated with an increased risk of developing drug abuse/d ependence. During this ontogenetic phase, brain and hormonal systems are st ill undergoing crucial maturational rearrangements, which take place togeth er with significant modifications in psychosocial development. However, the neurohormonal and behavioral facets of adolescence have been poorly invest igated in relation to the vulnerability to psychostimulants such as MDMA (" Ecstasy") and amphetamine (AMPH). Novelty-seeking, a temperamental/behavior al trait that is typical of this age period, might substantially contribute to both psychological and psychobiological vulnerability. In humans, an el evated score of novelty-sensation seeking and a derangement of monoaminergi c function were both associated with late adolescence MDMA users compared t o controls. In animal models of periadolescence, the search for novel stimu li and sensations actually shares a common neurobiological substrate (the r eward-related brain mesolimbic pathways) with psychostimulants. The present review summarises recent work in mice, which indicates that periadolescent subjects are characterized by an unbalanced and "extremes-oriented" behavi or and by elevated novelty-seeking compared to adults. Repeated and intermi ttent administration of cocaine or AMPH was associated with the development of a prominent locomotor sensitization in periadolescents, which failed to exhibit the marked sensitization of the stereotyped behavioral syndrome-po ssibly associated with poor welfare-that was typical of adults. A unique pr ofile of integrated behavioral and physiological hyporesponsivity to both f orced novelty and acute AMPH administration during periadolescence was also found. As a whole, these results, together with previous work on this topi c, suggest that periadolescents may be more "protected" from AMPH-related a versive properties, and perhaps more vulnerable to the experience of intern al states of reward, than older animals. Thus, the present animal model of adolescence seems to represent a reliable and useful method for the investi gation of vulnerability to a variety of habit-forming agents or emotional e xperiences whose positive reinforcing properties may rely on common neurobi ological substrates. A deeper understanding of psychostimulant effects duri ng adolescence on the complex interaction between genetic, neurobiologic, p sychosocial, and environmental factors will lead to earlier and more effect ive prevention and treatment. (C) 1999 Elsevier Science Ltd. All rights res erved.