Rodent Models of Adolescent Alcohol and Drug Self- Administration: Implications for Understanding Adult Substance Abuse

In humans, experimentation with drugs (including alcohol) typically begins in adolescence. Adolescent experimentation can escalate to abuse and dependence in adulthood. Converging evidence from molecular, cellular and systems analyses demonstrate adolescence as a plastic period of brain development when important modifications occur in reward pathway signaling. Environmental factors, including exposure to drugs, have the potential to impact these critical neurodevelopmental changes. Rodent models offer well-controlled and cost-effective methods of assessing neurobiological and longitudinal effects. This paper reviews research on drug self-administration during adolescence and subsequent propensity for abuse in adulthood as determined by rodent models. Self-administration studies report increased drug intake in adolescent rats, independent of changes in ingestive behavior. Some longitudinal studies report that adolescent drug use leads to increased consumption during adulthood, but results are variable. Behavioral tests following alcohol and nicotine report attenuated negative effects such as motor impairment, and increased positive effects such as association with reward in adolescents. Studies of “response cost” suggest that adolescents may experience greater subjective reward from direct dopamine agonists like cocaine, but may perceive lower levels of reward from non-dopaminergic drugs like alcohol, nicotine, and heroin. Collectively, research demonstrates that drug abuse spikes during adolescence in humans and rodents, and this may be due to increases in risk-taking and sensation-seeking which characterize adolescence in these species. However, drug use declines significantly through early adulthood in most organisms, with only certain “high risk” populations engaging in continued abuse and addiction as adults. Future studies should focus on elucidating 1) neurobiological differences between high and low adolescent users, and 2) the neurobiological underpinnings of the decrease in drug use that consistently occurs during adulthood, in an effort to discover possible identification, prevention, and treatment measures for the subpopulation of adolescents who exhibit abuse and addiction disorders into adulthood.