Models for the Prevention and Treatment of Drug Abuse

点击翻译按钮获取中文摘要

DESCRIPTION: (Provided by Applicant): The overall objective of this K05 application is to obtain salary support that will release time from teaching and administrative duties that are not directly related to research. This would effectively increase time allocated to research from the current 40 percent to 75-90 percent. An overview of the candidate?s 27 year background in drug abuse research is provided including a list of publications, presentations, a citation analysis, a record of research funding, mentorship of students, science advocacy and other educational activities. A section on career goals describes short- and long-term plans that will be implemented when more time is released for research, specific activities (including collaborations) that are planned to sustain outstanding research performance, how past and future goals are blended, the likelihood of continuing successful contributions, and plans to obtain and provide instruction on the responsible conduct of science. The research plan consists of continuing 2 R01 projects that have been funded by NIDA for over 20 years and beginning a third project, a new R01 that is under review. The first grant is a nonhuman primate model to study factors that affect the vulnerability to drug abuse (e.g., sex, hormonal status, duration of expsoure) and behavioral and pharmacological treatments that reduce drug abuse. Behavioral economic analyses that maximize treatment effects will be a procedural focus at the proposed experiments. The overall hypothesis for this series of experiments is that vulnerability factors such as sex and duration of exposure to drug self-administration will predict greater reinforcing efficacy. With respect to treatment effects, it is hypothesized that females will show a greater suppression of drug self-administration than males. The second grant to be conducted in rats, concerns genetic and other biological determinants of drug abuse such as other excessive behaviors (e.g., exercise and consumption of nondrug substances), sex, and hormonal status. These factors will be compared during critical transition phases of addiction; acquisition and reinstatement of drug seeking after drug access has been terminated. This research is based on the hypothesis that a predisposition (individual differences) for excessive behavior directed toward novel stimuli increases vulnerability to drug abuse, and that rats showing greater vulnerability to drug abuse will be more susceptible to treatment. The third grant, also to be conducted in rats, is focused on factors underlying escalation of drug abuse. The overall hypothesis is that if rats are given the opportunity to engage in excessive behavior directed toward nondrug substances (e.g. sucrose) or events (e.g., wheel running), they will show cross-sensitization to drug seeking behavior as measured by models of acquisition, escalation, regulation/dysregulation and reinstatement. There will be comparisons across species, gender, several drugs of abuse, routes of administration, and phases of the addiction process. The results should allow for identification of biological, behavioral and environmental factors that lead to recognition of individuals who are at risk for drug abuse, and the experimental interventions used with these models will inform prevention and treatment strategies for humans.