Sex Differences in Adolescent Vulnerability to Morphine

Georgia State University, Atlanta GA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): [unreadable] [unreadable] The adolescent phase of development is a particularly vulnerable period during which experimentation with drugs reaches a lifetime high, often initiating a problematic trajectory from recreational use to uncontrollable dependence on drugs such as opiates. Although the majority of drug abusers in the U.S. are male, an increasing number of women are drug dependent, and females are 4-5 times more likely than males to abuse opioidergic prescription pain killers. Yet only recently have adolescent and female subjects been tested in research using animal models to explore drug-seeking behavior. Therefore, age- and sex-related differences in vulnerability to drug abuse are unexplained. Moreover, potential risk factors which differentiate between adolescents who initiate the drug dependence trajectory vs. those who do not remain unexplored. Factors contributing to adolescent drug intake are likelly to include prior stress or trauma; adverse neonatal environments clearly increase drug addiction in adulthood. However, the specific impact of neonatal trauma on opiate self-administration in adolescent males and females is not known. Experiments proposed in this application will use behavioral techniques to test these hypotheses: (1) adolescent drug vulnerabilities extend to the reinforcing effects of morphine; (2) neonatal injury via hindpaw injection of an inflammatory agent results in elevated morphine self-administration in both male and female adolescent rats; and (3) that these effects are exacerbated in females. These behavioral effects are hypothesized to be mediated by developmental changes and sexual dimorphisms in the anatomical and functional organization of opioidergic circuits in the brain, which we will test in future experiments using cellular and molecular techniques. Together these studies will provide a biological basis whereby an adverse neonatal environment potentiates adolescent vulnerabilities to drug abuse in males and females. [unreadable] [unreadable]