Linda P. Spear

Transitions Into Underage and Problem Drinking: Developmental Processes and Mechanisms Between 10 and 15 Years of Age

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.

Motivational Systems in Adolescence: Possible Implications for Age Differences in Substance Abuse and Other Risk-Taking Behaviors.

Adolescence is an evolutionarily conserved developmental phase characterized by hormonal, physiological, neural and behavioral alterations evident widely across mammalian species. For instance, adolescent rats, like their human counterparts, exhibit elevations in peer-directed social interactions, risk-taking/novelty seeking and drug and alcohol use relative to adults, along with notable changes in motivational and reward-related brain regions. After reviewing these topics, the present paper discusses conditioned preference and aversion data showing adolescents to be more sensitive than adults to positive rewarding properties of various drugs and natural stimuli, while less sensitive to the aversive properties of these stimuli. Additional experiments designed to parse specific components of reward-related processing using natural rewards have yielded more mixed findings, with reports of accentuated positive hedonic sensitivity during adolescence contrasting with studies showing less positive hedonic affect and reduced incentive salience at this age. Implications of these findings for adolescent substance abuse will be discussed.

Nicotine-induced conditioned place preference in adolescent and adult rats

About 1 million American adolescents start smoking every year. Adolescents may be unusually sensitive to certain consequences of nicotine, demonstrating, for instance, significantly higher rates of dependence than adults at the same level of nicotine use. To explore whether adolescents may be more sensitive to rewarding properties of nicotine than adults, the present study used an animal model to assess the rewarding effects of a low nicotine dose (0.6 mg/kg) in a conditioned place preference (CPP) paradigm. Locomotor activity during conditioning and testing was also evaluated. Nicotine was observed to induce place preference conditioning in adolescent Sprague-Dawley rats, whereas the training dose of 0.6 mg/kg failed to produce convincing place preference in their adult counterparts. Age differences were also apparent in terms of nicotine influences on motor activity, with adults being more sensitive to nicotine-suppressant effects and only adolescents showing an emergence of nicotine-stimulatory effects upon repeated exposures. An increased predisposition to stimulatory nicotine effects during adolescence may contribute to age-specific rewarding properties of the drug as revealed using the CPP paradigm in this experiment. Increased sensitivity to stimulatory and rewarding effects during adolescence could potentially contribute to the high rate of nicotine use and dependence among human adolescents.

Underage Drinking: A Developmental Framework

A developmental framework for understanding and addressing the problem of underage alcohol consumption is presented. The first section presents the rationale for a developmental approach, including striking age-related data on patterns of onset, prevalence, and course of alcohol use and disorders in young people. The second section examines the fundamental meaning of a developmental approach to conceptualizing underage drinking. The third section delineates contemporary principles of developmental psychopathology as a guide to future research and intervention efforts. Strategic, sensitive, and effective efforts to address the problem of underage drinking will require a developmentally informed approach to research, prevention, and treatment.

Cocaine Effects on the Developing Central Nervous System: Behavioral, Psychopharmacological, and Neurochemical Studies

IMPLICATIONS and FUTURE DIRECTIONS. The data we have collected thus far support the following conclusions: 1. Subcutaneous administration of cocaine results in dose-dependent increases in brain and plasma cocaine in both dams and fetuses, and maternal plasma levels in the range of or above those observed in human cocaine users. Fetal levels are lower than those of the dam, suggesting that the placenta may partially restrict cocaine entry into the fetus. Concentrations of the active cocaine metabolite benzoylecgonine, however, are greater in fetal than in maternal brain; this may have important implications for brain development given the calcium-binding properties of this metabolite. 2. Chronic subcutaneous administration of 10, 20 or 40 mg/kg cocaine from E8-E20 does not alter litter size, body weights at birth or weaning, or development of reflexes or physical landmarks in the offspring. 3. Offspring exposed gestationally to cocaine exhibit learning and/or retention deficits in some but not all conditioning situations. 4. Behaviorally and psychopharmacologically, there is evidence for a potential attenuation in DA activity in preweanling pups exposed gestationally to cocaine. There is, however, no sign of any alteration in DA turnover in treated offspring sacrificed at weaning, although preliminary data suggest that DA levels may be increased in exposed pups during the neonatal period. Possible alterations in DA receptor function are currently being assessed. We are still at the initial stages of our work, and the data we have collected thus far have raised as many questions as they have answered. We plan to assess further the cognitive deficits observed in cocaine-exposed offspring. Under what contingencies are these learning and/or retention deficits observed, and are they permanent deficits or does recovery eventually occur? Is there actually an attenuation in DA activity in treated offspring? If so, is this attenuation related to compensations at the presynaptic and/or postsynaptic level, and what is the time course for this effect on the DA system? What are the critical periods for the production of these alterations; is cocaine exposure during the second or third trimester alone sufficient? How do our results compare with those of other laboratories that are using other methods for administering cocaine during gestation? At some point in the future we also hope to examine potential therapeutic approaches to reduce the cognitive deficits observed in exposed offspring.(ABSTRACT TRUNCATED AT 400 WORDS)

Anxiogenic effects during withdrawal from acute ethanol in adolescent and adult rats

Elevated signs of anxiety are observed in adult rodents during withdrawal from chronic as well as acute ethanol exposure. To determine whether adolescents, in addition to their insensitivity to a number of acute ethanol effects, might likewise be hyposensitive to these anxiogenic manifestations of withdrawal from an acute ethanol challenge, the behavior of adolescent and adult male Sprague-Dawley rats was assessed in an elevated plus maze (EPM) 18 h following intraperitoneal challenge with 4 g/kg ethanol. Adult but not adolescent animals demonstrated evidence of anxiety in the plus maze during acute ethanol withdrawal. To ensure that this finding did not merely reflect age differences in ethanol clearance, clearance times at each age were determined, with additional adolescents tested at the same time postclearance as the adults were previously. Adolescents still failed to demonstrate anxiogenic signs of withdrawal. Suppression of activity during the withdrawal test, however, was evident in animals of both ages. A relative resistance to the anxiogenic effects associated with acute ethanol withdrawal during adolescence could serve as a permissive factor for development of binge drinking patterns among human adolescents.

Effects of prenatal cocaine exposure on behavior during the early postnatal period.

Offspring of Sprague-Dawley dams injected SC with 40 mg/kg/3 cc cocaine HCl daily from gestational days 8-20, pair-fed dams injected with the vehicle alone and nontreated control dams were examined behaviorally during the early postnatal period. No significant differences were observed among the treatment conditions in maternal weight gain during pregnancy, duration of pregnancy, or number of live male and female pups/litter. Offspring body weights at birth and weaning, physical maturation and reflex development were not significantly affected by prenatal cocaine exposure. In contrast, neonates exposed prenatally to cocaine were observed to exhibit significant deficits in learning of an odor/milk association that nontreated offspring learned and retained for a 24 hr period. On postnatal day 12, cocaine offspring exhibited an increase in locomotor activity and attenuated wall climbing precipitated by footshock, in the absence of any alteration in sensitivity to footshock. Given that wall climbing has been previously shown to be strongly related to levels of catecholamine activity at this age, these data suggest the possibility that there may be some attenuation in catecholaminergic function in pups exposed gestationally to cocaine. The results of this study provide evidence that prenatal cocaine exposure may have an impact upon behavioral and cognitive function even during the early postnatal period. More work is needed to fully characterize the range of alterations observed and the neural mechanisms underlying these early exposure effects.

Heightened stress responsivity and emotional reactivity during pubertal maturation: Implications for psychopathology

This commentary reviews and reflects on the studies of this special section: studies that collectively provide compelling evidence for meaningful changes in stress- and emotionally reactive psychophysiological systems with the transition from middle childhood into adolescence. The observed changes were complex and often overlaid upon ontogenetic differences in basal levels of activation of these systems. Maturational increases in responsiveness to stressors were stressor dependent and differentially expressed across autonomic and hormonal measures. Pubertal status increased the impact of some affective valence manipulations, although not significantly influencing others, including negative affect-related potentiation of startle/reflexes. Such ontogenetic increases in stressor and affect sensitivity may have implications for developmental psychopathology. Developmental increases in stressor reactivity may normally aid youth in responding adaptively to the challenges of adolescence, but may result in stress dysregulation among at-risk adolescents, increasing further their vulnerability for psychopathology. Pubertal-related increases in sensitivity to emotionally laden stimuli may exacerbate individual predispositions for exaggerated affective processing, perhaps contributing to the emergence of psychological disorders in these youth. Together, these studies, with their innovative use of autonomic, reflexive, and hormonal measures to index age- and pubertal-related changes in reactivity to stressors and affective stimuli, provide promising directions for future research. Some of these, along with a few cautionary notes, are outlined.

Rewards, aversions and affect in adolescence: emerging convergences across laboratory animal and human data.

The adolescent transition is associated with increases in reward- and sensation-seeking, peer-directed social interactions, and risk-taking, with exploratory use of alcohol and other drugs often beginning at this time. These age-related behaviors may have biological roots embedded in the evolutionary past, with similar adolescent-typical characteristics evident across a variety of mammalian species. Drawing across human behavioral and fMRI data and studies conducting in laboratory animals, this review examines processing of rewards, aversions, and affect in adolescence. Evidence for both hyper- and hypo-reactivity during adolescence in the processing of rewards is reviewed, along with possible contributors to these differences. Indications of sometimes heightened reward reactivity during adolescence are contrasted with frequent attenuations in adolescent sensitivity to aversive stimuli. At the same time, adolescents appear particularly prone to becoming emotionally aroused, especially in social contexts. Emerging evidence hints that exaggerated adolescent reactivity in reward and affective systems may be promoted in part by unusual strong cross-reactivity between these systems during adolescence. Such age-related propensities may promote adolescent risk taking, especially in social and exciting contexts, and contribute to adolescent-typical propensities to attach greater benefit and less cost to risky behaviors such as alcohol and drug use than individuals at other ages.

Social Behavior and Social Motivation in Adolescent Rats: Role of Housing Conditions and Partner's Activity

The present study investigated 1) the effects of individual and grouped housing on social investigation, social contact behavior, and play behavior in adolescent rats tested with low socially active (grouped) and high socially active (isolated) play partners; and 2) the effects of long-term (8 days) and short-term (24 h) isolation on social behavioral manifestations and social motivation in terms of preference or avoidance of play partners. Social isolation of adolescent rats activated play behavior and social behaviors different from play, but play was predominantly affected under the conditions of this study. Long-term isolation was more effective than short-term, and resulted in greater manifestation of play and social preference. Adolescent rats were able to modify their social behaviors in response to social activity of the play partner: in isolated animals exposed to low socially active group-housed partners, play behavior was transformed into social activities unrelated to play; exposure of group-housed adolescents to high socially active previously isolated partners resulted in an increase of play behavior. Testing that allowed avoidance of social contacts revealed a dissociation between manifestations of play behavior and social motivation: group-housed play partners of isolated animals showed elevated levels of play behavior but a tendency to avoid their isolated pairmates.