Neurocognitive Consequences of Adolescent Drug Use

Behavioral disinhibition is a common characteristic associated with early-onset (i.e., adolescent) substance abuse. Our understanding of the etiological role of behavioral disinhibition in adolescent substance use remains unclear. Significant neuroanatomical development occurs throughout adolescence and into young adulthood. Such neuroanatomical changes pose particular challenges for studying neurocognitive consequences of drug abuse during this stage of development. Prolonged drug exposure during adolescence could impede the formation of frontal lobe circuitry, resulting in impairments in the regulation and control of behavior. However, such impairments might be difficult to detect because of their subtle emergence over prolonged drug exposure and potential masking effects from the developmental melioration associated with the maturation of frontal lobe systems during adolescence. Consequently, many neurocognitive impairments might not be detected until young adulthood. This R21 application proposes studies designed to identify inhibitory-based, neurocognitive impairments, both as antecedent deficits evident prior to the onset of adolescent drug use, and as resultant deficits following a history of adolescent drug use. The research examines how the expression of these deficits may also be mediated by two established adolescent risk factors for substance abuse, attention deficit hyperactivity disorder (ADHD) and conduct disorder (CD). The project also examines the long-standing hypothesis that adolescent drug use could alter sensitivity to the acute neurocognitive and subjective-rewarding effects of abused drugs. Dose-challenge studies will examine how acute sensitivity to neurocognitive and rewarding effects of abused drugs is associated with a history of adolescent drug use and ADHD/CD. The proposal capitalizes on ADHD and CD as well-established risk factors for adolescent drug use and seeks to determine the functional mechanisms underlying this risk using recent neurocognitive and psychophysiological techniques to identify specific inhibitory-based neurocognitive deficits that could contribute to the maintenance and escalation of drug use into young adulthood. The collaborative proposal draws on investigative expertise in developmental psychopathology, cognitive neuroscience, and behavioral pharmacology.