ADOLESCENT DRUG ABUSE: BRAIN DEVELOPMENT, COGNITION, AND VULNERABILITY
Evidence for Enhanced Neurobiological Vulnerability to Nicotine During Periadolescence in Rats
Pier Vincenzo Piazza, M.D., Ph.D.
[Slides not available]
Epidemiological studies indicate that there is an increased likelihood for the development of nicotine addiction when cigarette smoking starts during early adolescence. These observations suggest that adolescence could be a critical ontogenetic period during which drugs of abuse have distinct effects responsible for the development of dependence later in life. The long-term behavioral and molecular effects of repeated nicotine treatment were compared during either periadolescence or postadolescence in rats. It was found that exposure to nicotine during periadolescence, but not postadolescence, increased the intravenous self-administration of nicotine and the expression of distinct subunits of the ligand-gated acetylcholine receptor in adult animals. Both these changes indicated an increased sensitivity to the addictive properties of nicotine. In conclusion, adolescence seems to be a critical developmental period characterized by enhanced neurobehavioral vulnerability to nicotine.
Adolescent Brain and Behavior: Age-Related Sensitivities to Natural Rewards and Drugs
Linda P. Spear, Ph.D.
Adolescence is associated with certain age-typical behaviors evident across species, including increases in novelty-seeking/risk-taking and elevated peer-directed social interactions, along with highly conserved transformations in a variety of brain regions. Prominent brain regions sculpted during adolescence include the mesocorticolimbic regions critical for attributing motivational incentives, affective relevance, and hedonic value to natural rewards as well as drugs of abuse. These ontogenetic changes in the brain may contribute to the unique behavioral characteristics of adolescents by influencing the reward value of the stimuli they encounter. Using conditioned place preference (CPP) paradigms, the responses to and relative preferences for social stimuli, novel objects, and nicotine were examined in adolescent and adult rats. Exploration of novel objects during conditioning was greater in adolescent rats, with adolescent males showing stronger novel object CPP than adult males. Social CPP also was stronger in adolescents, emerging in both group- and isolate-housed adolescents, while only being evident in isolate-housed adults. Nicotine-induced CPP was evident only in adolescent animals at the training dose used (0.6 mg/kg), with the stimulatory effects of nicotine likewise emerging during conditioning only in adolescents. Although some dissociations between reward value (as indexed by CPP preference scores) and seeking behaviors (e.g., the time spent with stimuli during conditioning) emerged in these data sets, social stimuli, novel objects, and nicotine generally were found to be more rewarding for adolescents than adults.
Vulnerabilities in Neurocognitive Processes in Adolescence
Beatriz Luna, Ph.D.
Risk-taking behavior is one of the primary causes for health problems and mortality in adolescence, due in great part to flawed decisionmaking. Decisionmaking requires the ability to choose and implement the responses that best fit goal-directed behavior. Adolescence is the period of initial transition to mature cognitive control of behavior that is supported by important brain maturation processes, such as synaptic pruning and myelination. The interaction between cognitive development and brain maturation, however, is poorly understood. Dr. Luna presents studies that characterize the changes in behavior and brain function that underlie the maturation of cognitive control of behavior, as measured by the ability to voluntarily inhibit responses and to use working memory for goal-directed behavior.
Behavioral results indicate that by midadolescence adult levels of cognitive control become evident, while the mature use of working memory is not evident until late adolescence. fMRI results from Dr. Luna’s team indicated that the brain function supporting adult-level cognitive control in adolescents is different from that of adults. Although adolescents and adults recruited a similar brain network, adolescents relied primarily on the prefrontal cortex, while adults recruited the promoter-response planning regions and the hippocampus, freeing up valuable prefrontal executive processes.
Results suggest that although adolescents can appear to have mature cognitive control of behavior in a well-controlled environment, they need to exhaust brain resources used for high-level computation to a greater degree than adults. Using resources needed for cognitive control of behavior, as is provided by the prefrontal cortex, may set a system that is more vulnerable to the lack of cognitive control.
Brain Development in Healthy and Impulsive-Inattentive Children
Judith L. Rapoport, M.D.
[Slides not available]
Dr. Rapoport presented a prospective, longitudinal, anatomic brain MRI study that revealed considerable changes during childhood and adolescence and the influences of these changes. The study showed the relationship of brain developmental trajectories to age, gender, genetics (including some individual candidate risk genes), and IQ. For all these factors, the effect on the trajectory itself, rather than just regional volume, was striking—indicating that these periods of great change may also be periods of greatest vulnerability.
She also presented prospective anatomic and functional studies of children with attention deficit hyperactivity disorder that suggest important disorder-related changes at baseline and a plastic response, predicting a good outcome at followup.
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