Elevated Levels of Impulsivity and Reduced Place Conditioning With d-Amphetamine: Two Behavioral Features of Adolescence in Mice Walter Adriani and Giovanni Laviola Istituto Superiore di Sanita ` Human adolescents may have experience with easily available psychoactive drugs. Impulsivity and/or peculiarities in reward systems may play a role. These variables were studied in adolescent (Postnatal Day [PND] 30 – 49) and adult (PND  60) CD-1 mice. In Experiment 1 (impulsivity), food-restricted mice were tested in operant chambers with 2 nose-poking holes that delivered 1 food pellet immediately or 5 pellets after a delay, respectively. Delay length was increased over days (0 –100 s). Adolescent mice showed a shift to the left in the intolerance-delay curve, as well as enhanced demanding when nose-poking was not reinforced. In Experiment 2 (place conditioning with d-amphetamine at 0.0, 1.0, 2.0, 3.3, or 5.0 mg/kg for 3 days), adolescent mice showed no reliable evidence of place conditioning when compared with adults. Hence, 2 main features of adolescence were elevated impul- sivity and restlessness, and low (or absent) rewarding efficacy of amphetamine. Recent epidemiological research has emphasized that adoles- cence is associated with increased sensation seeking, reckless and risk-taking behavior (Arnett, 1992; Wilson & Daly, 1985), as well as the use of various kinds of psychoactive agents (Mathias, 1996). Adolescents ranging from 11–12 to 17–18 years of age are likely to start with tobacco smoking, which can be followed by marijuana and/or alcohol, and eventually psychostimulants as well as opiate drugs (see Yamaguchi & Kandel, 1984). The age of first encounter with these psychoactive compounds appears to be critical, as a higher probability to shift from use to abuse and to develop dependence appears to be associated with an early approach with drugs (Anthony & Petronis, 1995; Robins & Przybeck, 1985; for tobacco smoking, see Breslau, Fenn, & Peterson, 1993; Breslau & Peterson 1996; Taioli & Wynder, 1991). Despite the social and scientific importance of deepening our knowledge on this issue (see, e.g., Colby, Tiffany, Shiffman, & Niaura, 2000), there have been very few investigations dealing with the psychobiological factors involved in the expression of this particular behavioral repertoire (for a review, see Laviola, Adriani, Terranova, & Gerra, 1999; Spear, 2000). For the purpose of laboratory studies, a suitable animal model of human adolescence is available in rodents, in which adolescence is classically defined as the ontogenetic period that encompasses the week preceding the onset of puberty and the first few days there- after (Spear & Brake, 1983). During this period, brain monoam- inergic systems show dramatic changes in transmitter levels and activity (Loizou, 1972; Loizou & Salt, 1970), and midbrain, hip- pocampus, and cerebral cortex show proliferation and maturation of axon terminals and synapses (Andersen, Rutstein, Benzo, Hostetter, & Teicher, 1997; Andersen, Thompson, Rutstein, Hostetter, & Teicher, 2000; Santana, Rodriguez, Afonso, & Are- valo, 1992; Stamford, 1989; Teicher, Andersen, & Hostetter, 1995). Adolescent rodents also exhibit marked peculiarities in their spontaneous behavioral repertoire (Bronstein, 1972; Laviola, Ad- riani, Morley-Fletcher, & Terranova, 2002; Macrı `, Adriani, & Laviola, 2002; Meaney & Stewart, 1981; Panksepp, 1981; Primus & Kellogg 1989; Spear, Shalaby, & Brick, 1980; Terranova, Laviola, & Alleva, 1993; Terranova, Laviola, De Acetis, & Alleva, 1998). Such an animal model, if it has enough face and construct validity (see Spear, 2000), must be able to show (a) behavioral features that recall those found in human adolescents, (b) an elevated vulnerability to the consumption of drugs during adoles- cence, and (c) marked long-term consequences of such exposure. Elevated levels of novelty seeking (Adriani, Chiarotti, & Laviola, 1998) and risk taking (Macrı ` et al., 2002), as well as a reduced behavioral and hormonal response to stress (Adriani & Laviola, 2000; Choi & Kellogg, 1996; Choi, Weissberg, & Kellogg, 1997; Laviola et al., 2002) are exhibited by rodents around this age. Impulsivity is another behavioral feature of human adolescents that needs to be modeled in adolescent rodents. Different aspects of impulsivity can be studied with operant-behavior paradigms in laboratory settings. For example, it has been assumed that impul- sive subjects are intolerant to situations in which reward is delayed or uncertain. Smaller immediate reinforcers are preferred to larger Walter Adriani and Giovanni Laviola, Section of Behavioural Patho- physiology, Laboratorio Fisiopatologia O.S., Istituto Superiore di Sanita `, Rome, Italy. This research was supported as part of the research project “Psychobi- ological Risk or Protection Factors for Behavioural Disorders and Vulner- ability to Recreational Substances Abuse During Development” (intramu- ral grant to Giovanni Laviola), Istituto Superiore di Sanita `, and by the research project “Pathogenesis and Recovery in Animal and In-Vitro Models of Alzheimer Disease,” Italian Ministry of Health. Walter Adriani was supported by a G. Levi bursary from the Accademia Nazionale dei Lincei, Italy. We wish to thank C. Brabant for very precious help in the discussion of conditioning data, M. Sbragi for developing the computer software for the operant chambers, and A. Adriani for producing aluminum adaptors for the Coulbourn Instrument nose-poking devices. Correspondence concerning this article should be addressed to Giovanni Laviola, Section of Behavioural Pathophysiology, Laboratorio Fisiopato- logia O.S., Istituto Superiore di Sanita `, Rome, Italy. E-mail: Laviola@ iss.it Behavioral Neuroscience Copyright 2003 by the American Psychological Association, Inc. 2003, Vol. 117, No. 4, 695–703 0735-7044/03/$12.00 DOI: 10.1037/0735-7044.117.4.695 695