Peculiar Vulnerability to Nicotine Oral Self-administration in Mice during Early Adolescence

Abstract

(10 mg/l). After a 6-day period, a fading study was carried out, in which nicotine concentration was reduced to 7 mg/l (days 7-9) and 5 mg/l (days 10-12), to assess whether animals would compensate by increasing their intake from the nicotine solution. In Experiment 2, psychopharmacological effects on locomotion induced by the nicotine solution (0, 10, 30 mg/l) Recent research has emphasized that adolescence is associated with patterns of temporary deviance (Arnett 1992) and the use of various kinds of psychoactive agents (Mathias 1996). Drug abuse in adolescents ranging from 11-12 to 17-18 years of age is likely to start with tobacco smoking, which can be followed by marijuana and/or 1991;Breslau et al. 1993;Nides et al. 1995;Kandel and Chen 2000). Despite the social and scientific importance of deepening our knowledge of this issue (see e.g. Colby et al. 2000), there have been very few investigations on the psychobiological factors contributing to the specific adolescence-related willingness to experience various psychoactive drugs (for a review, see Laviola et al. 1999;Spear 2000). For the purpose of laboratory studies, a suitable animal model of human adolescence is available in rodents. Namely, periadolescence is classically defined as the ontogenetic period that encompasses the week preceding the onset of puberty and the first few days thereafter (Spear and Brake 1983). Periadolescent rodents differ markedly from adults in their spontaneous behavioral repertoire (Cirulli et al. 1996;Terranova et al. 1993;Meaney and Stewart 1981;Panksepp 1981). In fact, elevated levels of novelty seeking and a reduced behavioral and hormonal response to stress (Adriani et al. 1998;Adriani and Laviola 2000) are exhibited by animals around this age. A characteristic hyporesponsivity to the effects of an acute administration of psychostimulants (Spear and Brake 1983;Laviola et al. 1995;Bolanos et al. 1998;Adriani and Laviola 2000), a peculiar pattern of behavioral sensitization following repeated drug exposure (Laviola et al. 1995(Laviola et al. , 2001Adriani et al. 1998), as well as a weak drug-induced place conditioning profile (Adriani et al. 1998;Bolanos et al. 1996Bolanos et al. , 1998 but see Campbell and Spear 2000), are also reported. Based on these findings, an increased vulnerability to the addictive properties of abused drugs has been suggested to be typical of adolescence in both humans and animals models (see Laviola et al. 1999).In the present study, we were interested in nicotine, which beside being the main psychoactive compound implied in tobacco smoking, also shares most of the characteristics of other addictive drugs (Corrigall et al. 1992(Corrigall et al. ,1994Pontieri et al. 1996;Merlo-Pich et al. 1997;Stolerman 1999). Nicotine's effects in mice have been shown to be highly dependent on the genetic background (see Marks et al. 1989;Robinson et al. 1996). However, the interaction between the pharmacological effects and the incentive properties of nicotine during the adolescent period has been largel...

Dietary Restriction and Nicotine can Reduce Anxiety in Female Rats

“…Adolescents smoke significantly fewer cigarettes than adults, yet experience higher rates of dependence at the same levels of use (Kandel and Chen, 2000). In line with the human findings, much of the data gathered from animals also reflect a peculiar vulnerability to nicotine in adolescence (Laviola et al, 1999;Adriani et al, 2002). In mice, it seems that early adolescence in particular (during the period just preceding puberty) is the developmental phase responsible for the pattern of behaviors constituting sensitivity to nicotine's effects (Adriani et al, 2002).…”

Combined Exposure to Nicotine and Ethanol in Adolescent Mice Differentially Affects Anxiety Levels during Exposure, Short-Term, and Long-Term Withdrawal

“…C57BL/6 mice were chosen because prior reports demonstrate that adult and periadolescent mice from this strain consume nicotine in the concentration used in the present study. In fact, oral nicotine has also been shown to be effective in eliciting behavioral (Adriani et al, 2002(Adriani et al, , 2004Gaddnas et al, 2001) and neurochemical alterations, including nicotinic receptors upregulation (Nuutinen et al, 2005;Sparks and Pauly, 1999), altered monoamine levels, and metabolism (Gaddnas et al, 2000;Tammimaki et al, 2006;Vihavainen et al, 2006) as well as altered expression of genes implicated in synaptic plasticity induced by drugs of abuse (Marttila et al, 2006) and in Alzheimer's disease (Gutala et al, 2006) in this and other mouse strains. This strain of mice is known to present particular features, such as higher voluntary ethanol consumption (Crawley et al, 1997), which should be taken into consideration in studies that involve the administration of this substance, even though the bases underlying these strain-specific characteristics remain poorly understood (Crabbe et al, 1999).…”

Low dose nicotine treatment during early adolescence increases subsequent cocaine reward

“…We have used a brief exposure period and a low dose of nicotine, given by intravenous injection, in order to better model early teenage smoking than the modes of chronic administration used in previous studies [1,3,19]. Intravenous administration of nicotine is less stressful than subcutaneous or intraperitoneal injections, gives equivalent amounts of drug as the animal matures, and more closely mimics the pharmacokinetics of smoking.…”

“…When given a two bottle choice, early adolescent mice [postnatal day (P) were the only group to prefer nicotine solution over water [3]. In conditioned place preference (CPP) studies, periadolescent rats were shown to exhibit a highly significant preference for the nicotine-paired compartment whereas adult rats did not [6,47].…”