Administrative Core

Abstract: The key functions of the Administrative Core in CDART are to: (1) provide thematic scientific integration of the different projects around the personality constructs under investigation; (2) create synergy across the three proposed projects and other ongoing projects on campus; (3) facilitate interdisciplinary collaboration among basic and prevention sciences using both neurobehavioral and psychosocial levels of analysis; and (4) oversee the long-range goal of translating our basic research into the development and implementation of targeted prevention interventions. There are four specific aims in the Core: one scientific, one organizational, one that involves disseminating our research findings to practitioners in the field, and one that involves expanding leadership in the prevention science and drug abuse research communities. For the Scientific Aim, the Core will provide the structure necessary to produce publications that extend beyond the boundaries of the individual projects. The Core seeks to engender cross-cutting empirical, theoretical, and methodological articles that promote translation from basic science to prevention practice. For the Organizational Aim,the Core provides an intellectually stimulating and creative environment where the norm is to examine research questions and issues from a multilevel, interdisciplinary perspective. This will be accomplished by hosting a seminar series, inviting nationally-prominent seminar speakers, hosting an annual conference on issues relevant to CDART research, and having an annual retreat of key personnel and trainees. In terms of Dissemination of Results, the Core will disseminate the research findings obtained in the laboratory to the prevention/intervention being conducted by practitioners in the field. For the Leadership Aim,the Core will serve as a local, regional, national, and international resource, advocate, and leader for the translation of basic science into efforts to prevent drug use/abuse. This will be accomplished by building connections with other national NIDA-funded centers, sponsoring workshops and training conferences, and by having CDART faculty involved in professional organizations. The Core is also committed to providing training to the next generation of drug abuse prevention researchers.

Project 1: Individual Differences in Facets of Impulsivity: An Animal Model

Abstract: The central theme of CDART is that multiple facets of impulsivity defined by the UPPS scale of Whiteside and Lynam (2001) are related to different paths to drug use and that these paths are associated with different neurobiological mechanisms. To the extent that we can link specific behavioral tasks to these different self-report facets, animal models can be used to identify critical neural mechanisms that underlie the association between risk-related facets and drug use. A detailed understanding of the mechanisms that mediate the link between different facets of impulsivity and drug use will provide information about designing preventive interventions that target these risk-related facets. The overall goal of this preclinical project is to test two overarching hypotheses: (1) individual differences in the facets termed "urgency", "disinhibition" and "sensation seeking" are related most strongly to problem use, escalation and initiation respectively, as operationally defined within an animal model of drug self-administration; and (2) individual differences in urgency, disinhibition and sensation seeking are related most strongly to differences in amygdala, prefrontal cortex and nucleus accumbens respectively, as measured by in vitro neurochemistry and in vivo electrophysiology. The specific aims are to: Aim 1: Develop an animal model of urgency using a task similar to that developed in humans. Aim 2: Determine if individual differences in urgency, disinhibition and sensation seeking predict problem use, escalation and/or initiation of amphetamine self-administration, respectively. Aim 3: Determine if individual differences in facets of impulsivity differentially predict the ability of nondrug interventions to reduce use, escalation and/or initiation of amphetamine self-administration. Aim 4: Determine if individual differences in these risk-related facets of impulsivity are related to alterations in monoamine transporter function in amygdala, prefrontal cortex and/or nucleus accumbens. Aim 5: Determine if individual differences in these risk-related facets of impulsivity are related to altered patterns of neuronal activity in amygdala, prefrontal cortex and/or nucleus accumbens.

Project 2: Individual Differences in Drug Abuse Liability

Abstract: Prevention investigators in our Center and elsewhere have demonstrated that drug abuse prevention efficacy can be significantly enhanced by targeting individuals who are most vulnerable to developing problems and tailoring message content and format based on the characteristics of these individuals. Our previous work focused on drug use initiation and identified behavioral mechanisms (neurobehavioral response to reinforcing, novel and emotional stimuli) whereby the sensation seeking dimension of impulsivity is associated with vulnerability to drug use initiation and high sensation-value contexts enhance the efficacy of prevention interventions designed to reduce drug use initiation. Further development of laboratory models to identify individuals who are vulnerable to drug use escalation and development of associated problems and identifying the characteristics of these individuals that predispose them to vulnerability and/or influence the efficacy of targeted intervention materials is of critical importance for informing and advancing the field of drug abuse prevention. This application proposes five years of research to continue laboratory investigations of individual differences associated with drug use escalation and associated exposure to heavy drug use. Growing evidence suggests that vulnerability to drug-use escalation is associated with self-control mechanisms. A multidisciplimary approach combining personality measurement with laboratory abuse liability assessment, behavioral inhibition task performance and brain imaging methodologies will be used to examine impulsivity among matched groups of tobacco and marijuana users who have either maintained stable patterns of intermittent/light use (escalation resistant) or who have escalated to heavy use with and without extended histories of heavy use (escalation; escalation + extended drug exposure) to test the hypothesis that drug use escalation is associated with inhibitory neurobehavioral dimensions of impulsivity. Knowledge of the association between component dimensions of impulsivity and drug-use escalation will enhance understanding of vulnerability to and consequences of drug use escalation and thus our ability to design more efficacious tailored and targeted drug abuse prevention interventions

Project 3: Examining Urgency from Neurobiology to Prevention

Abstract: Impulsive behavior is an important contributor to substance misuse, which is prevalent in college samples. Our center (CDART) has identified four distinct personality traits that underlie impulsive behaviors: Negative Urgency (NU), lack of Premeditation (PRE), lack of Perseverance (PSV) and Sensation Seeking (SS). Our previous work clarified the roles of SS and PRE in substance misuse in the college population. In our more recent work, NU has emerged as an important and independent contributor to substance misuse. Even after controlling for SS and PRE, NU is related to the onset and escalation of substance misuse and other risky behaviors, and the relation between NU and alcohol use is mediated through different mechanisms than the relations for PRE and SS. Thus, our previous work clearly shows that understanding NU is critically important to the prevention of substance misuse in college populations. The four proposed studies will use a range of methods to investigate the nature of NU and the mechanisms through which it exerts its effects. Study 1 will identify underlying biological substrates of NU using fMRI. It is predicted that regions in the prefrontal cortex associated with inhibitory control will show less activation in high NU participants when participants are experiencing negative affect. Study 2 will identify the affective contexts and response characteristics most important to NU. It is predicted that affect will be more important to NU than to other impulsivity traits and that NU will manifest in impulsive behavior on tasks that include prepotent responses and/or tasks in which an impulsive response is negatively reinforced. Study 3 will examine the interactions among impulsivity traits, affective contexts, and interpersonal contexts in predicting impulsive behavior in daily life. It is predicted that NU will be related to impulsive behavior when high NU participants are under the influence of negative mood. Other impulsivity traits, like SS, may be more responsive to interpersonal contexts. Study 4 will test whether an intervention designed to help high NU participants respond more adaptively to their negative affect can reduce future impulsive behavior. It is predicted that mindfulness training will reduce impulsive behaviors among high NU individuals but not among high SS individuals.

Statistics and Psychometrics Core (SPC)

Abstract: The new Statistics and Psychometrics Core (SPC) for the University of Kentucky’s Center for Drug Abuse Research Translation (CDART) grew out of demand for quantitative services provided previously in the Administrative Core. The SPC will expand and formalize the roles of the statisticians and methodologists with whom CDART investigators and graduate student / postdoctoral researcher trainees have collaborated for years. The functions fulfilled by these statisticians and methodologists will include: (i) consultation on study design and data analysis, ranging from discussions at CDART committee and project meetings to one-on-one / small-group assistance provided in person and through electronic correspondence; (ii) direct performance of data analysis, both cross-sectional and longitudinal, that apply appropriate statistical methodology requiring special expertise in statistical computing or conversance with mathematically technical concepts relevant to prevention scientists; (iii) co-authorship on manuscripts presenting new scientific findings, entailing not only preparation of narrative for data analysis directly performed but also broader oversight of manuscript content to ensure lucidity and technical accuracy; (iv) outreach to the larger prevention, psychological, and neurobehavioral research communities through co-organization of a workshop for a national audience and manuscripts acquainting investigators with state-of-the-art methodology; (v) instruction to trainees on data analysis and statistical computing, both through scheduled methodology for one-on-one / small-group assistance provided in person and through electronic correspondence; and, (vi) assistance in psychometric evaluation and development of measurement instruments, including both self-report questionnaires and behavioral tasks.

Training and Pilot Core

Abstract: The new Training and Pilot Core for the Center for Drug Abuse Research Translation (CDART) has the specific goal of encouraging trainees to develop, implement and evaluate evidence-based preventive interventions that rely on multi-disciplinary perspectives and research. The central theme of CDART is that different facets of impulsivity (urgency, disinhibition and sensation seeking) are associated most strongly with different phases of drug use/abuse (problem use, escalation and initiation, respectively). As a key component of CDART, this core will require trainees to build bridges that connect different areas of research and translate basic research into prevention practice. Pilot investigators will be encouraged to design and implement preventive interventions that fit within the CDART theme. Thus, we will expand and formalize the roles of training and pilot project development through the following Specific Aims: 1) Provide the structure to train graduate students and postdoctoral scholars in translational research relevant to drug abuse prevention; 2) Promote and manage our pilot project program that introduces faculty and research associates to translational research relevant to drug abuse prevention and CDART’s research mission; 3) Identify promising minority candidates for recruitment into the training and pilot project programs relevant to drug abuse prevention. As part of the approach, pre- and post-doctoral trainees will be introduced to the field of drug abuse prevention, with a special emphasis on translational work by attending and presenting in monthly trainee data presentations, attending seminars by researchers in drug abuse, and retreats designed to “brainstorm” with CDART faculty about future research plans, taking relevant topic-specific courses and ethics in research training, and attending informal seminars. The pilot program will prioritize early career investigators and minority scholars for funding, as well as more advanced faculty new to the drug abuse field. Proposals will be required to demonstrate the relevance of the project to the science and practice of drug abuse prevention. As a result, CDART trainees and pilot project principal investigators will be prepared to take lead roles in bridging the gap between basic and applied researchers.