PERINATAL POLYDRUG ABUSE--COCAINE AND ALCOHOL

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One of the most commonly abused drug combinations is that of alcohol and cocaine. Such polydrug ingestion may adversely affect the mother and her offspring more than the consumption of ethanol or cocaine alone. The potent CNS drugs which readily cross the blood-brain barrier also cross the placenta, and their pharmacological actions can impair fetal and prenatal development. The principal objectives of this research proposal are: 1) to examine whether co-administration of alcohol and cocaine during the perinatal period alters the disposition, pharmacodynamics and toxicity, of ethanol or cocaine and its metabolites in the mother and fetus; 2) to evaluate the pregnancy outcome with long-term Co-administration of cocaine and alcohol during the reproductive period throughout repeated pregnancies in the first as well as the second and third generation of animals; and 3) to determine the long-term effect on neurobehavior, growth and developmental outcome in the offspring after exposure to cocaine and alcohol throughout gestation. We intend to mimic the real life situation of the mother ingesting alcohol and cocaine on a once per day basis throughout gestation. We feel strongly that such a "naturalistic" design will be more informative than constant exposure. Our hypotheses are fivefold: 1) Co-administration of ethanol and cocaine may alter the disposition and pharmacodynamics of Cocaine in the maternal- fetal unit due to production of ethylbenzoylecgonine (cocaethylene), a metabolic product of the co-administration of alcohol and cocaine; 2) The decreased distribution of blood flow to certain organs produced by Cocaine may be aggravated by the strong vasoconstrictive action of cocaethylene; 3) Cocaethylene is more potent than benzoylecgonine, a major cocaine metabolite, and may accumulate longer than the cocaine alone in the mother, causing prolonged adverse effects. These adverse effects may be further prolonged by the continued ethyl ester formation from benzylecgonine derived from demethylation and deethylation of Cocaine on cocaethylene which will result in accumulation of this compound for protracted periods of time; 4) Long-term exposure of cocaine with alcohol throughout consecutive pregnancies may increase the incidence of adverse sequelae on the offspring due to slow elimination of cocaethylene; and 5) The pregnancy outcome may he worsened in the second or third generation of animals born to a drug exposed mother. Cocaine, ethanol, or both, as well as cocaethylene will be infused intravenously to our established chronically implanted conscious rat model, which will provide a physiologic condition to assess pharmacokinetic-dynamic and behavioral effects of the drugs in the maternal-fetal unit. The long-term behavioral effects of perinatal drug exposure will also be evaluated. The data obtained from these studies will contribute to a greater understanding of the risk of polydrug abuse during pregnancy and reproductive period.GRANT=R01DA07356 Anabolic steroid (AS) use has many detrimental health effects. Nevertheless, adolescent use, especially among those engaged in high school (HS) football, is increasing. AS availability has varied between 32 and 60%, with use increasing from 1.1% to 5.7% during the period 1987-1991 in the Portland, Oregon metropolitan area. During 1987, for every 36 HS football players claiming steroid availability, one student used AS. This increased to one player using AS for every 6 reporting availability in 1991. Over 250,000 adolescents are using or have used AS in the United States. The aim of this proposal is to develop and evaluate a school- based AS prevention program designed to prevent initiation and use of AS and other drugs among high risk adolescents. The intervention is based on five years of prospective prevention research and uses a multidimensional, cognitive-behavioral approach, including knowledge of AS, promoting AS alternatives (nutrition and exercise), and resistance and communication skill training. The program intervenes at the individual, peer, adult and-environmental levels. In study years 02, 03, 04 and 05, all students engaged in football at 36 high schools will be randomly assigned by school to one of two groups: l) a 20 session intervention: l2 in a classroom setting and 8 weekly exercise training periods or 2) a minimum information control. Intervention components will be delivered by coaches, peers and certified athletic trainers. The intervention will be repeated annually for new players, with additional yearly booster sessions for returning athletes during years 03, 04 and 05. Coaches, parents and peer educators will receive instruction on program objectives and implementation. Questionnaires will be administered prior to and after the intervention and at year-end follow-up, to assess availability, knowledge, attitudes, intent to use and use of AS and other drugs. Attitudes and behaviors concerning nutrition and exercise will be examined, along with demographics, resistance skills, environmental factors, intrapsychic constructs peer influences and anthropometric measures. Program implementation and its effects will be assessed by audiotape, observation and surveys. The link between mediators targeted by the program components and reduction of drug use will be studied. The relationship of intervention components with positive and negative outcomes (knowledge, attitudes, intent and behaviors) will be determined. The study will identify protective and risk factors for AS use and provide an understanding of how and under what conditions AS use can be prevented.