To successfully negotiate the developmental transition between youth and adulthood, adolescents must maneuver this often stressful period while acquiring skills necessary for independence. Certain behavioral features, including age-related increases in social behavior and risk-taking/novelty-seeking, are common among adolescents of diverse mammalian species and may aid in this process. Reduced positive incentive values from stimuli may lead adolescents to pursue new appetitive reinforcers through drug use and other risk-taking behaviors, with their relative insensitivity to drugs supporting comparatively greater per occasion use. Pubertal increases in gonadal hormones are a hallmark of adolescence, although there is little evidence for a simple association of these hormones with behavioral change during adolescence. Prominent developmental transformations are seen in prefrontal cortex and limbic brain regions of adolescents across a variety of species, alterations that include an apparent shift in the balance between mesocortical and mesolimbic dopamine systems. Developmental changes in these stressor-sensitive regions, which are critical for attributing incentive salience to drugs and other stimuli, likely contribute to the unique characteristics of adolescence. ᭧

a b s t r a c tInhaled aerosol dose models play critical roles in medicine, the regulation of air pollutants and basic research. The models fall into several categories: traditional, computational fluid dynamical (CFD), physiologically based pharmacokinetic (PBPK), empirical, semi-empirical, and "reference". Each type of model has its strengths and weaknesses, so multiple models are commonly used for practical applications. Aerosol dose models combine information on aerosol behavior and the anatomy and physiology of exposed human and laboratory animal subjects. Similar models are used for in-vitro studies. Several notable advances have been made in aerosol dose modeling in the past 80 years. The pioneers include Walter Findeisen, who in 1935 published the first traditional model and established the structure of modern models. His model combined aerosol behavior with simplified respiratory tract structures. Ewald Weibel established morphometric techniques for the lung in 1963 that are still used to develop data for modeling today. Advances in scanning techniques have similarly contributed to the knowledge of respiratory tract structure and its use in aerosol dose modeling. Several scientists and research groups have developed and advanced traditional, CFD, and PBPK models. Current issues under study include understanding individual and species differences; examining localized particle deposition; modeling non-ideal aerosols and nanoparticle behavior; linking the regions of the respiratory tract airways from nasal-oral to alveolar; and developing sophisticated supporting software. Although a complete history of inhaled aerosol dose modeling is far too extensive to cover here, selected highlights are described in this paper.

Purpose The purpose of this paper is to outline notable alterations occurring in the adolescent brain, and consider potential ramifications of these developmental transformations for public policy and programs involving adolescents. Methods Developmental changes in the adolescent brain obtained from human imaging work are reviewed, along with results of basic science studies. Results Adolescent brain transformations include both progressive and regressive changes that are regionally specific and serve to refine brain functional connectivity. Along with still maturing inhibitory control systems that can be overcome under emotional circumstances, the adolescent brain is associated with sometimes elevated activation of reward-relevant brain regions, whereas sensitivity to aversive stimuli may be attenuated. At this time, the developmental shift from greater brain plasticity early in life to the relative stability of the mature brain is still tilted more towards plasticity than seen in adulthood, perhaps providing an opportunity for some experience-influenced sculpting of the adolescent brain. Conclusions Normal developmental transformations in brain reward/aversive systems, areas critical for inhibitory control, and regions activated by emotional, exciting and stressful stimuli may promote some normative degree of adolescent risk-taking. These findings have a number of potential implications for public policies and programs focused on adolescent health and well-being.

The behavior and psychopharmacological sensitivity of periadolescent rats are examined in this review. Periadolescent rats are hyperactive and engage in more conspecific play behavior than younger or older rats. When compared with other-aged rats, periadolescents exhibit enhanced performance in simple active-avoidance learning tasks, but perform poorly in more complex appetitive and avoidance learning tasks in which increases in locomotor activity do not improve performance, perhaps as a result of age-specific alterations in selective attention or stimulus processing. Such behavioral "anomalies" of periadolescent animals observed in traditional laboratory situations may be in some way adaptive when considered in the context of the animals' natural habitat. In terms of psychopharmacological responsiveness, periadolescent rats, when compared with younger or older animals, are less sensitive to catecholaminergic agonists but are more responsive to the catecholaminergic antagonist haloperidol. This pattern of psychopharmacological sensitivity suggests that the catecholaminergic systems may be temporarily hyposensitive during the periadolescent period. Evidence is presented that a negative feedback system in the form of dopamine autoreceptors may become functionally mature in mesolimbic brain regions during the periadolescent period. The possibility is presented that maturation of these self-inhibitory autoreceptors might result in a temporary decrease in the efficacy of mesolimbic dopamine projections, perhaps contributing to the psychopharmacological and behavioral characteristics of periadolescent animals. In support of this suggestion, evidence is reviewed indicating that the behavior of adult animals with lesions of the ventral tegmental area, a region containing cell bodies from which these mesolimbic dopaminergic projections originate, resembles that of periadolescent rats.

Numerous developmental changes occur across levels of personal organization (eg, changes related to puberty, brain and cognitive-affective structures and functions, and family and peer relationships) in the age period of 10 to 15 years. Furthermore, the onset and escalation of alcohol use commonly occur during this period. This article uses both animal and human studies to characterize these multilevel developmental changes. The timing of and variations in developmental changes are related to individual differences in alcohol use. It is proposed that this integrated developmental perspective serve as the foundation for subsequent efforts to prevent and to treat the causes, problems, and consequences of alcohol consumption. D URING THE DEVELOPMENTAL period spanning 10 to 15 years of age, considerable changes occur in biological, cognitive, emotional, and social processes, as well as physical and social contexts. These changes occur across different levels of personal organization, including overt physical appearance (eg, increases in physical size), refinements in the structure and function of the central nervous system (CNS), and maturational changes in the internal hormonal and neurophysiological milieus. By age 10, most adolescents have begun the rapid changes of puberty, as defined by changes in secretory patterns of the gonadal steroids. These hormonal changes are accompanied by dramatic changes in height as well as readily visible changes in body composition and secondary sexual characteristics, with overt physical differences between the genders becoming increasingly apparent.Whereas some personal changes are closely aligned with chronological age, such as attendance at elementary, middle, or high school, others are more closely tied to variations in the timing of events (pubertal onset) and/or developmental stages, such as interest in the opposite gender and relative peer influences. As a result, different aspects of personal development take place at different times, and different individuals mature in different dimensions at different times. For example, pubertal development may occur at a different time than does the socialcognitive development necessary for intimate relationships. The physical and emotional changes associated with pubertal development occur over a considerable age range. Adolescents who begin puberty relatively early may experience processes postulated to be associated with puberty, such as heightened emotional states and greater influences of external stimuli, sooner than they have the cognitive and emotional abilities to control consistently behaviors that develop as a function of the maturation of brain regions and collaborative brain networks.The average age of puberty has decreased over the past century, whereas the average age of assumption of adult roles has increased because of prolonged education by more youths and later age of initial marriage. These changes have heightened the significance of understanding adolescence along the multiple continua of physical, cogniti...

The results of this experimental series demonstrate that adolescent animals consume significantly more ethanol than adult animals under a variety of home cage continuous-access circumstances, with the relatively greater intake of adolescents further magnified by a number of test conditions. Subtle experimental details often thought to be innocuous can have a substantial impact on overall amount of voluntary ethanol consumption observed in both adolescent and adult animals.

Social interactions have been shown to be rewarding for adolescent and adult rats; however, there has been little emphasis on comparing the strength of the rewarding value of social stimuli across ontogeny. Since age differences in social interactions may vary with sex or housing circumstances, the present study assessed social conditioned place preference (CPP) in adolescent and adult male and female Sprague-Dawley rats housed either socially or in isolation and conditioned with either group-housed or isolate-housed partners. Isolated animals of both sexes and ages demonstrated social CPP, with the strongest preference emerging in adolescent males. Social CPP was not evident in group-housed adults whereas group-housed adolescents developed a preference for the compartment previously paired with similarly housed partners; however, when socially housed adolescents were conditioned with isolated partners, social CPP did not emerge. Age differences in social CPP may reflect age-related neural alterations in brain systems implicated in regulation of social behavior.

Per occasion, alcohol consumption is higher in adolescents than in adults in both humans and laboratory animals, with changes in the adolescent brain probably contributing to this elevated drinking. This Review examines the contributors to and consequences of the use of alcohol in adolescents. Human adolescents with a history of alcohol use differ neurally and cognitively from other adolescents; some of these differences predate the commencement of alcohol consumption and serve as potential risk factors for later alcohol use, whereas others emerge from its use. The consequences of alcohol use in human adolescents include alterations in attention, verbal learning, visuospatial processing and memory, along with altered development of grey and white matter volumes and disrupted white matter integrity. The functional consequences of adolescent alcohol use emerging from studies of rodent models of adolescence include decreased cognitive flexibility, behavioural inefficiencies and elevations in anxiety, disinhibition, impulsivity and risk-taking. Rodent studies have also showed that adolescent alcohol use can impair neurogenesis, induce neuroinflammation and epigenetic alterations, and lead to the persistence of adolescent-like neurobehavioural phenotypes into adulthood. Although only a limited number of studies have examined comparable measures in humans and laboratory animals, the available data provide evidence for notable across-species similarities in the neural consequences of adolescent alcohol exposure, providing support for further translational efforts in this context.