Role of HPA Axis in Adolescent Vulnerability to Drug Addiction

Duke University, Durham NC

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Abstract

DESCRIPTION (provided by applicant): A small percentage of people who experiment with addictive substances become drug addicts. Addiction is the result of the interaction among an addictive substance, a vulnerable individual and his/her environment. If we could predict which users are most likely to become addicts and learn what environmental variables are most likely to precipitate addiction, we could more successfully target prevention efforts. It is well-known that users who begin drug-taking in early adolescence are more likely to become addicts than those who wait until late adolescence or adulthood. Furthermore, it is well known that stress and the stress hormones corticosterone and corticotrophin releasing factor (CRF) promote initial drug seeking and relapse in abstinent users, and are protective against the aversive effects of drugs of abuse. We hypothesize that the developing HPA axis contributes to developmental vulnerability to drug abuse in adolescents. We have obtained preliminary data to suggest that adolescents as a group have elevated HPA axis activity compared to adults, and that those adolescents with the highest levels of this activity are the most likely to initiate drug seeking. We now propose to determine whether adolescents in general or those adolescents with the most reactive stress systems are more susceptible to the addictive effects of drugs of abuse and less susceptible to the aversive effects. We will prescreen adolescent and adult rats for their behavioral and neuroendocrine responses to stress before evaluating their behavior in tasks related to cocaine's reinforcing effects, withdrawal effects, and development of addiction-like behaviors. We will use self-administration with extended training and DSM-IV modeled tests for addiction to assess drug reinforcement and addiction. In separate experiments, we will use the light-dark task to assess whether age-of-onset and stress reactivity predict severity of withdrawal-induced anxiety. These studies will assess whether adolescence is truly a vulnerable period for development of addiction.