A unique hormonal and behavioral hyporesponsivity to both forced novelty and d-amphetamine in periadolescent mice

The identification of critical ontogenetic periods of increased vulnerabili ty to the effects of drugs of abuse could have a great psychobiological and clinical-therapeutical importance. Potential age-related differences in th e response of the hypothalamic-pituitary-adrenal (HPA) axis to both stress and psychostimulants has been tested here in an animal model of adolescence . Periadolescent (PND 33;43) and Adult (PND>60) mice of both sexes were inj ected with d-amphetamine (AMPH; 0, 2, or 10 mg/kg i.p.) and immediately fac ed with a mild psychological stress experience, i.e.placement in a novel en viroment. A detailed time-course analysis of both hormonal and behavioral p rofiles was performed, with animals being sacrificed for trunk-blood collec tion sit different time-points during the test (before the injection, NT gr oup; 15, 30, or 120 min after the injection). Basal corticosterone (CORT) l evels (NT group) were consistently higher in periadolescents than in adults . As a whole, a marked increment of blood CORT levels was found in mice of both ages exposed to forced novelty. However, important age-related differe nces were also observed, with Saline-injected periadolescents still exhibit ing elevated levels of locomotion at the end of the 120-min test: session a nd failing to show the increasing profile of CORT release over the baseline that was typical of adults. Upon an AMPH 2 administration, periadolescents exhibited a much lower profile of locomotor hyperactivity than adults, and also failed to show an increase across the course of the session in CORT r elease, that was observed in adults. When treated with the high AMPH. 10 do se, a marked locomotor hyperactivity was found in periadolescents, which ho wever showed much lower levels of the stereotyped licking and gnawing behav ior, that was typical of adults. The present results suggest a unique profi le of integrated behavioral and physiological hyporesponsivity in mice duri ng periadolescence. The latter also represents a very useful model for the study of the issue of psychobiological risk factors involved in vulnerabili ty to drugs of abuse in human adolescents. (C) 2000 Elsevier Science Ltd. A ll rights reserved.