Novelty seeking as well as amphetamine sensitization were studied in adult (postnatal day "PND" > 60) and periadolescent (PND 3343) mice treated with saline or amphetamine (2 or 10 mg/kg once per day) for 3 days in a familiar environment. After a 48-hr wash-out period, mice were challenged with either saline or amphetamine (2 mg/kg) in the same environment. When given a choice, animals showed a preference for a novel environment, an effect more marked in periadolescents. Acute amphetamine strongly increased novelty seeking in adults, whereas it had an opposite effect in periadolescents. Adult mice in the chronic amphetamine 2 group showed a conditioned preference for the drug-paired compartment, whereas an aversion characterized adult mice in the amphetamine 10 group. Periadolescents in the latter group exhibited a greater sensitization of the locomotor response, but did not show the compulsive licking typical of adults. This appears to be a useful model to study psychobiological risk factors involved in vulnerability to addiction during human adolescence.

Adolescence comes in association with puberty, when maturation and rearrangement of major neurotransmitter pathways and functions are still taking place. The neurobiological processes occurring in the brain during this developmental period have been so far poorly investigated. Yet, it is during adolescence that some major neuropsychiatric disorders may become evident, including ADHD, schizophrenia, and drug abuse. Moreover, the age-related neurobehavioural plasticity renders adolescents particularly vulnerable to the consequences of psychoactive drug exposure. In this view, there is an increased likelihood that addiction will develop when psychoactive drug use starts early during adolescence. From all these observations adolescence emerges as a critical phase in development. In the present review, we focus on recent neurobiological characterization of adolescent rats and mice. As for vulnerability to addictive behaviour, nicotine exposure during adolescence dose-dependently down-regulated levels of AMPA GluR2/3 subunits in the striatum, suggesting a reduced neurobehavioural plasticity in adult subjects. Comparable exposure during adulthood had opposite effects. It was found consistently that exposure to nicotine during adolescence, but not similar exposure in the post-adolescent period, increased the expression of specific subunits of the acetylcholine receptor in adult rats, thus enhancing the reinforcing efficacy of nicotine in a self-administration paradigm. The present data identified a specific age-window, characterized by long-term effects on behavioural and neurochemical indexes, of vulnerability. With respect to potential therapeutic approaches in ADHD, we studied the adolescent spontaneously-hypertensive-rat (SHR) in an intolerance-to-delay operant-behaviour paradigm. The model was further validated by the finding that impulsivity was reduced by chronic methylphenidate administration. Impulsive SHR animals were characterized by reduced cannabinoid CB1 receptor density in the prefrontal cortex. Interestingly, an acute cannabinoid agonist increased levels of self-control behaviour in these animals. The present data suggest that pharmacological modulation of the cannabinoid system might improve some behavioural anomalies seen in ADHD. In conclusion, modelling the adolescent phase in rats and mice appears to be useful for the investigation of determinants of vulnerability to addiction and to other early-onset neuropsychiatric disorders.

Epidemiological studies indicate that there is an increased likelihood for the development of nicotine addiction when cigarette smoking starts early during adolescence. These observations suggest that adolescence could be a "critical" ontogenetic period, during which drugs of abuse have distinct effects responsible for the development of dependence later in life. We compared the long-term behavioral and molecular effects of repeated nicotine treatment during either periadolescence or postadolescence in rats. It was found that exposure to nicotine during periadolescence, but not a similar exposure in the postadolescent period, increased the intravenous self-administration of nicotine and the expression of distinct subunits of the ligand-gated acetylcholine receptor in adult animals. Both these changes indicated an increased sensitivity to the addictive properties of nicotine. In conclusion, adolescence seems to be a critical developmental period, characterized by enhanced neurobehavioral vulnerability to nicotine.