Health and Developmental Consequences of Youth Drug Abuse

Research Findings from February, 2004 Director's Report

This section lists selected summaries from NIDA funded research projects that investigate the developmental implications of drug use. The summaries provided were selected from recent issues of the Director's Report to the National Advisory Council on Drug Abuse. For a more comprehensive listing of NIDA funded projects see the Director's Report.

Nicotine Self-Administration In Adolescent and Adult Female Rats

A rat model was used to determine the impact of the age of onset on nicotine self-administration. In Experiment 1, nicotine self-administration of female Sprague-Dawley rats over a range of acute doses (0.01-0.08 mg/kg per infusion) was determined in adolescent (beginning at 54-62 days) versus adult (beginning at 84-90 days). In Experiment 2, chronic nicotine self-administration over 4 weeks from adolescence into adulthood was compared with the chronic self-administration beginning in adulthood. In Experiment 3, adolescent-adult differences in nicotine effects on body temperature and locomotor responses were determined. Adolescent-onset rats showed increased nicotine intake compared with adult-onset rats in an eight-fold range of acute unit doses/infusion. Significant age differences were also seen in the chronic level of nicotine self-administration. Over 4 weeks, the adolescent-onset group had nearly double the rate of nicotine self-administration of the benchmark nicotine dose (0.03 mg/kg per infusion) compared to the adult-onset group. This increased nicotine intake persisted into adulthood. Adolescent rats had a significantly greater response than adults to the hypothermic effects of nicotine, but had significantly less response than adults to the reduction in locomotor activity seen after nicotine. Thus, adolescent-onset nicotine self-administration in female rats was associated with significantly higher levels of nicotine self-administration versus rats that began nicotine self-administration in adulthood. This greater self-administration persists into adulthood and may underlie greater propensity of adolescents to nicotine addiction. Levin, E.D., Rezvani, A.H., Montoya, D., Rose, J.E. and Swartzwelder, H.S. Adolescent-Onset Nicotine Self-Administration Modeled In Female Rats. Psychopharmacology, 169(2), pp.141-149, 2003.

Exposure to Amphetamine or Cocaine Limits the Ability of Later Environmental Enrichment to Promote Structural Plasticity in the Brain

Drugs of abuse and many other kinds of experiences share the ability to alter the morphology of neuronal dendrites and spines, the primary site of excitatory synapses in the brain. Dr. Terry Robinson, Dr. Brian Kolb and colleagues hypothesized that exposure to psychostimulant drugs might influence later experience-dependent structural plasticity. They treated rats repeatedly with amphetamine or cocaine and then housed them in either a complex environment or standard laboratory cages for 3-3_ mo. The brains were processed for Golgi-Cox staining, and the number of dendritic branches and density of dendritic spines on medium spiny neurons in the nucleus accumbens and pyramidal cells in the parietal cortex were quantified. On most measures, prior treatment with amphetamine or cocaine interfered with the ability of experience in a complex environment to increase dendritic arborization and spine density, which occurred in the untreated controls. Studies of humans who have used psychostimulants for long periods indicate that they have neuropsychological deficits that persist during abstinence. These deficits are usually attributed to either neurotoxic effects of the drugs or their ability to render specific brain areas dysfunctional. However, the data from the current study suggest an alternative way in which drug use might produce persistent behavioral and cognitive deficits, by impairing the ability of specific neural circuits to change as a result of experience. On a more positive note, if exposure to psychostimulant drugs can alter the effects of subsequent experience, then experience may be able to influence the later effects of drugs. In fact, there is evidence from animal studies that early environmental enrichment can be protective against the effects of psychostimulant drugs in adulthood. Kolb, B., Gorny, G., Li, Y., Samaha, A.N., and Robinson, T.E. Amphetamine or Cocaine Limits the Ability of Later Experience to Promote Structural Plasticity in the Neocortex and Nucleus Accumbens. Proceedings of the National Academy of Sciences, USA, 100, pp. 10523-10528, 2003.

Preliminary Evidence of Hippocampal Dysfunction in Adolescent MDMA (Ecstasy) Users

Dr. Leslie Jacobsen and colleagues published the results of an exploratory study designed to assess the potential cognitive and neurobiological effects of the use of MDMA in adolescence. Six adolescent MDMA users and six non-using adolescents that were matched on age, gender, IQ, and other drug use were asked to perform a series of tasks that tested their attentional and memory capabilities. In tests that measured performance on simple, selective, and divided attention tasks, MDMA users were found to have significantly longer reaction times, but no differences in accuracy. Adolescent MDMA users were found to differ in hippocampal activation pattern during working memory tasks from non-using adolescents, but this difference was only present at the most difficult level of the tasks, and was also found to be greatest among those individuals that had most recently used MDMA. This study is the first to demonstrate these differences among adolescent MDMA users that, when compared with the majority of users studied as adults, have comparatively little lifetime exposure to the drug. Jacobsen, L.K., Mencl, E.W., Pugh, K.R., Skudlarski, P. and Krystal, J.H. Preliminary Evidence of Hippocampal Dysfunction in Adolescent MDMA ("ecstasy") Users: Possible Relationship to Neurotoxic Effects. Psychopharmacology, DOI: 10.1007/s00213-003-1679-4, November 28, 2003.

Marijuana Use Affects Completion of High School

Cross-sectional research has shown a link between adolescent substance use and educational motivation. The purpose of the current study was to examine this link in a longitudinal sample of African American youth. The study examined the interrelationships between alcohol and both marijuana use and school motivation over the high school years and their effect on graduation in 681 African American adolescents (50.8% female). School motivation was shown to relate to subsequent alcohol use throughout high school and marijuana use early in high school. School motivation did not affect graduation status, but alcohol and marijuana use were related to a lower likelihood of graduating from high school. Some gender differences and differences among those who had tried alcohol or marijuana at the first wave as opposed to those who had not tried each substance were found. The findings support a systems model where school experiences can affect substance use, which, in turn, can affect the completion of high school. Zimmerman, M.A., Schmeelk-Cone, K.H. A Longitudinal Analysis of Adolescent Substance Use and School Motivation Among African American Youth. J Res Adolesc, 13(2), pp. 185-210, 2003.