REVIEWSWindows of vulnerability to psychopathology and therapeutic strategy in the adolescent rodent modelAdriani, W.; Laviola, G.Author Information Behavioural Neuroscience Section, Dept. Cell Biology and Neuroscience, Istituto Superiore di Sanità, viale Regina Elena 299, I-00161 Roma, Italy Sponsorship: These studies were supported by the Research Project on ‘Hypoxic-ischemic brain damage in the newborn’ (Ministry of Health, Italy) to G.L.; by a ‘Marie Curie’ Fellowship (European Community) and by a ‘Young Investigator Award’ (Agenzia 2000, CNR, Italy) to W.A.; and by Sigma-Tau SpA, Pomezia, Italy. Correspondence and requests for reprints to G. Laviola Behavioural Neuroscience Section, Dept. Cell Biology and Neuroscience, Istituto Superiore di Sanità, viale Regina Elena 299, I-00161 Roma, Italy e-mail: [email protected] Received 7 April 2004 Accepted as revised 31 May 2004 Behavioural Pharmacology: September 2004 - Volume 15 - Issue 5 - p 341-352 Buy Abstract 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. © 2004 Lippincott Williams & Wilkins, Inc.