Linda A. Dykstra - US grants

Opioids are the most effective drugs known for the relief of pain; however, their clinical utility is limited by a number of undesirable effects such as the production of tolerance, physical dependence and a tendency to be abused. A considerable amount of research has been devoted to developing opioid analgesics with low physical dependence and abuse liabilities. In this regard, the partial agonists and the agonist-antagonists have shown some utility as analegics; however, the dysphoric effects of some of these drugs has limited their use. The aim of the experiments proposed here is to examine the behavioral pharmacology of selected partial agonists and mixed agonist-antagonists as analgesics. This will be done by examining a number of drugs under a shock titration procedure in squirrel monkeys and making comparisons between compounds in terms of the shape of their dose-effect curves, the ease with which they are antagonized and the occurrence of cross tolerance among them. Compounds selected for examination include the partial agonists buprenorphine and picenadol, the putative kappa agonists bremazocine, nalbuphine and U-50, 488 and the separate isomers of the sigma agonist n-allyl normetazocine. These compounds will be examined alone and in the presence of various opioid antagonists thought be have varying activity at mu, kappa or delta receptors. In addition, the nonopioid analgesic clonidine will be examined. Finally, the type of stimulus used to assess analgesia will be examined as a determinant of drug effect.

DESCRIPTION (provided by applicant): There is growing evidence that the N-methyl-D-aspartate (NMDA) class of the glutamate receptor modulates the effects of a number of drugs of abuse. Therefore, it is likely that a deeper understanding of interactions of the NMDA system with drugs of abuse will inform the search for treatment interventions, both in relationship to drug dependence and pain modulation. The proposed experiments explore the mechanisms underlying interactions between the NMDA system and opioid analgesics using an integrative strategy that combines genetic, pharmacological and behavioral approaches. The genetic approach employs an animal model of NMDA deficiency that consists of partial deletion of the gene encoding the essential NR1 subunit of the NMDA receptor (NR1-/- mice). The pharmacological approach explores interactions between drugs of abuse and a range of NMDA antagonists in mice of the C57BL/6 background strain. Both the genetic and the pharmacological approaches are used to investigate several prominent behavioral effects of opioid analgesics, namely their antinociceptive, conditioned and reinforcing effects. Specific Aim 1 examines the role of NMDA receptors in opioid antinociception and tolerance, employing two different antinociceptive assays: the hot plate procedure and the tail withdrawal procedure. Specific Aim 2 investigates the role of NMDA receptors in the conditioned effects of morphine and other opioid analgesics using the conditioned place preference procedure (CPP) and Specific Aim 3 investigates in the reinforcing effects of opioid agonists using a drug self-administration procedure. Preliminary experiments indicate the feasibility of using these approaches in our own laboratory. Collectively, the specific aims test the hypothesis that the antinociceptive and reinforcing effects of morphine and other opioid analgesics are altered in NR1-/- mice as compared to WT controls and that morphine's effects are altered by the administration of selective NMDA antagonists in two background strains of mice, C57BL/6 and 129/SvEv.

The objective of this Research Scientist Award is to free Dr. Dykstra of the majority of her administrative and teaching responsibilities so that she can devote her time to a research program focused on the opioid analgesics. In particular emphasis will be placed on compounds which may provide effective pain relief, but with reduced dependence potential. These include buprenorphine, selected kappa agonists and several mixed agonist- antagonists. Analgesic effects will be examined in the squirrel monkey shock titration procedure and in rodent thermal discrimination procedure. For comparison, several other behavioral endpoints will be examined, including schedule-controlled, complex conditional discriminations and drug discrimination behavior. In all of these investigations, emphasis will be placed on the relationship between the behavioral effects of opioid agonists and presumed activity at mu and kappa opioid receptor types. In order to draw relationships between these effects, comparisons will be made on the basis of 1) differing behavioral profiles and potency relationships amongst various opioid agonists 2) the potency of opioid antagonists in attenuating effects of these agonists and 3) the occurrence of cross tolerance between them.

Although a wealth of evidence suggests an interaction between the opioid and immune systems, very few studies have investigated the role of behavioral and environmental variables in this interaction. One variable of particular importance in understanding long-term opioid use and relapse relates to the ease with which many of the effects of opioid administration and withdrawal can be conditioned to stimuli in the environment. Accordingly, it is likely that the alterations in immune function which occur as the result of acute as well as long-term opioid administration might also become conditioned and therefore have the potential to persist long after opioid use has been terminated. Thus, it is our objective to examine opioid-induced alterations in immune function with emphasis on the role of behavioral, environmental, and pharmacological variables in these interactions. Our first specific aim provides background information for these investigations by exploring the unconditioned effects of acute and chronic opioid administration. These investigations include a range of doses of the opioid agonist morphine, given either acutely (one daily dose) or chronically (one daily dose for 1,3,5 or more days). Immune function will be assessed with several different rodent in vitro assays, including mitogen-stimulation of splenic, lymph node and whole-blood lymphocytes, a natural-killer cell assay, assessment of interleukin-1, interleukin-2 and interferon production and flow cytometry analysis to assess alterations in leukocyte subpopulations. Additional in vivo measures of antibody production will also be employed. Our second specific aim examines the role of conditioning in opioid-induced alterations in immune function. Given previous demonstrations that stimuli paired with opioid administration can elicit many of the signs and symptoms of opioid administration as well as modulate the development of tolerance to opioid effects, we will determine whether stimuli associated with morphine will induce morphine-like alterations in immune function (in the absence of morphine) and also whether stimuli associated with morphine administration will modulate the effects morphine has on immune function. The retention and extinction of these conditioned alterations in immune function will also be examined. Our third specific aim investigates the mechanisms which underlie interactions between morphine-induced alterations in immune function and behavioral/environmental events. These studies will employ selective antagonists to examine the role of opioid and catecholaminergic systems in opioid-induced alterations in immune function. In all studies, pharmacological variables such as dose of morphine, and duration of morphine administration will be assessed as well as behavioral/environmental variables such as the nature of the conditioning environment, the number of conditioning trials and preexposure to the conditioning stimuli.

The objective of this Research Scientist Award is to free Dr. Dykstra of the majority of her administrative and teaching responsibilities so that she can devote her time to a research program focused on the opioid analgesics. In particular emphasis will be placed on compounds which may provide effective pain relief, but with reduced dependence potential. These include buprenorphine, selected kappa agonists and several mixed agonist- antagonists. Analgesic effects will be examined in the squirrel monkey shock titration procedure and in rodent thermal discrimination procedure. For comparison, several other behavioral endpoints will be examined, including schedule-controlled, complex conditional discriminations and drug discrimination behavior. In all of these investigations, emphasis will be placed on the relationship between the behavioral effects of opioid agonists and presumed activity at mu and kappa opioid receptor types. In order to draw relationships between these effects, comparisons will be made on the basis of 1) differing behavioral profiles and potency relationships amongst various opioid agonists 2) the potency of opioid antagonists in attenuating effects of these agonists and 3) the occurrence of cross tolerance between them.

Research efforts in medicinal chemistry have produced opioid and nonopioid analgesics which may provide effective pain relief with reduced dependence potential. It is our objective to examine the analgesic effects of a number of these compounds with emphasis on agonists presumed to have activity at mu or kappa opioid receptor types. Analgesic activity will be assessed with 2 procedures, the squirrel monkey shock titration procedure and a newly developed thermal discrimination procedure in rats. In addition, studies will be carried out in which the intensity of the nociceptive stimulus (shock or heat) is manipulated in order to determine 1) the extent to which the effects of mu or kappa agonists depend on stimulus intensity and 2) whether analgesic effects might be revealed for less efficacious compounds at lower stimulus intensities. For comparison, we will also examine the effects of several mu and kappa opioid agonists on schedule- controlled behavior. These investigations will be carried out in squirrel monkeys, rats and pigeons so that differences in drug effects between species can be examined. In addition, the discriminative stimulus properties of mu and kappa opioid agonists will be investigated in rats and pigeons. In all of these studies, emphasis will be placed on the relationship between the behavioral effects of opioid agonists and the mediation of their effects through different opioid receptor types. In order to draw such relationships, opioid agonists will be examined alone, in combination with opioid antagonists and in animals made tolerant to mu or kappa agonists. Comparisons will then be made on the basis of 1) differing behavioral profiles and potency relationships among the opioid agonists 2) the potency of opioid antagonists in attenuating the effects of these agonists and 3) the occurrence of cross tolerance among them.

science education; university student; African American; curriculum; university; Native Americans;

This multi-user biology equipment proposal requests funds to purchase a cryostat that will be used in a variety of research projects in the Psychology Department at University of North Carolina - Chapel Hill. The user group consists of four faculty with active research programs who are members of the Experimental and Biological Psychology Program (Gallagher, Lysle, Dykstra) and the Developmental Psychology Program (Gariepy). In addition, three of the users are members of the Neurobiology Curriculum faculty (Gallagher, Lysle, and Dykstra). The proposed cryostat will replace an American Optical cryostat purchased in 1984 at a cost of $5,016, which can no longer be serviced/maintained. The refrigeration unit of the existing cryostat contains CFCs that do not meet current standards. Parts for this machine also can no longer be replaced. The new equipment will provide facilities for the continued conduct of research projects for which the existing cryostat has been used. In addition, the new cryostat will have the precision needed for a number of projects for which the existing cryostat has been inadequate. For example, when uniform section thickness is crucial for quantitative work (e.g. using iodinated ligands) the investigators have had to arrange for time on a cryostat in the medical school. The purchase of a new cryostat with high precision for tissue sectioning will allow all research to be conducted within our multi-user facility. The proposed purchase is for a Leica 3000 cryostat with dual compressor and motorized handwheel ($28,625) and height adjustment module (additional $2,360). Thirty percent of the total cost will be provided from equipment funds in the Psychology Department (see attached letter in appendix from the Psychology Department Chair). As described in the detailed Description of Research, the applications for which a cryostat is needed range from standard histological methods to molecular neurobiological research. These latter inclu de studies using quantitative methods for in vitro autoradiography, mapping of labelled oligonucleotides administered in vivo and in situ hybridization histochemisty. In addition to serving the needs of the faculty within the user group, the equipment will also be extensively used in research training at undergraduate, graduate and postdoctoral levels.

DESCRIPTION: (Applicant's Abstract) The College on Problems of Drug Dependence (CPDD) will hold its 60th Annual Scientific Meeting at the Scottsdale Princess Resort in Scottsdale, Arizona, from June 13 through June 18, 1998. There will be 5 days of scientific sessions which will be made up of volunteer oral presentations, poster sessions, and 12 or 13 timely symposia. Special attention is given to the needs of young scientists, trainees, students, and underrepresented populations in the field. Such attention is needed to insure a continued cadre of scientists for the field of drug abuse. There will be a good balance of all fields and topics representing the drug abuse research community. Although final symposia choices will not be made by the Program Committee of CPDD until the fall of 1997, among the list of symposia and chairs that have already been submitted and are under consideration by the Program Committee are the following: Anandamide: Toward an understanding of its physiological role(s), Billy Martin Effect of nocicieptin (orphanin FQ) on opiod-regulated pain thresholds, Alan Gintzler The drug abuse relevance of recent research on excitatory amino acid neurotransmission, Robert Balster Is scheduling always necessary? Model post marketing surveillance program for abuse liability, Theodore Cicero and Sidney Schnoll The Drug Evaluation Committee of the CPDD: Current status and future directions, William Woolverton and Charles France Continency management for real-life drug abuse treatment, Leslie Amass and Martin Iguchi Fundamental processes of human infant development affected by prenatal cocaine exposure, Bernard Karmel Plenary and award lectures as well as several satellite meetings and specialty workshops will complete the program. The Proceedings will be published as an archival NIDA monograph and will be mailed to all meeting registrants and to all NIDA grantees.

Recent studies indicate that the effects of opioid analgesics can be modulated by interactions between opioid as well as nonopioid receptor systems. For example, the N-methyl-D-aspartate (NMDA) receptor system has been shown to be involved in both the acute effects of morphine as well as in the development of morphine tolerance. Although a wealth of studies have examined interactions between opioid and NMDA receptor systems, very little is known about the behavioral mechanisms that underlie these interactions. Therefore, the studies proposed here examine NMDA/opioid interactions in a complex behavioral paradigm, the squirrel money shock titration procedure. This procedure is particularly appropriate for these studies because it provides a way to differentiate the contribution of discriminative and response variables in NMDA/opioid interactions. In addition, studies are proposed to examine pharmacological mechanisms that are important in NMDA/opioid interactions. In particular, investigations will examine NMDA-induced alterations in the effects of opioids that differ from morphine in terms of their relative efficacy. These investigations employ the squirrel monkey titration procedure as well as a rodent tail withdrawal procedure which can be altered so it reveals activity for opioids with low efficacy relative to morphine.

science education; Hispanic Americans; African American; health science research support; university student; role model; university; curriculum; clinical research;

Recent studies indicate that the effects of opioid analgesics can be modulated by interactions between opioid as well as nonopioid receptor systems. For example, the N-methyl-D-aspartate (NMDA) receptor system has been shown to be involved in both the acute effects of morphine as well as in the development of morphine tolerance. Although a wealth of studies have examined interactions between opioid and NMDA receptor systems, very little is known about the behavioral mechanisms that underlie these interactions. Therefore, the studies proposed here examine NMDA/opioid interactions in a complex behavioral paradigm, the squirrel money shock titration procedure. This procedure is particularly appropriate for these studies because it provides a way to differentiate the contribution of discriminative and response variables in NMDA/opioid interactions. In addition, studies are proposed to examine pharmacological mechanisms that are important in NMDA/opioid interactions. In particular, investigations will examine NMDA-induced alterations in the effects of opioids that differ from morphine in terms of their relative efficacy. These investigations employ the squirrel monkey titration procedure as well as a rodent tail withdrawal procedure which can be altered so it reveals activity for opioids with low efficacy relative to morphine.

DESCRIPTION (provided by the applicant): The Graduate School of the University of North Carolina at Chapel Hill (UNC-CH), along with two historically black universities, North Carolina A&T State University (NC A&T SU) and North Carolina Central University (NCCU), are submitting an application to renew our Bridges to the Future Program for another three-year period. As sister institutions in the North Carolina State system, these three institutions have a long track record of working together. The Partnership of Under-Represented Scientists United for Education (PURSUE) Program represents our joint commitment to increase the production of minority scholars in the biomedical sciences. The main focus of our Bridges Program is to facilitate the transition of underrepresented minority students from masters degree granting institutions to doctoral degree granting institutions. Most of the core ideas that are presented in this proposal were implemented and evaluated in our current Bridge Program and therefore build on its success. All of the objectives of the initial program are on course with the majority of the students either still progressing toward a masters degree or already transferred to a Ph.D. program in the biomedical sciences. The renewal of our Bridge program is built on the following successful strategies: 1) Students are drawn from a large pool of underrepresented students, 2) The program is designed in response to continuous feedback from the enrolled students, 3) All students are assigned multiple mentors and advisors from the participating institutions, 4) Skill building workshops are provided as needed by individual students, 5) A full time coordinator mediates student concerns, assists with recruitment, organizes seminars and disseminates information, 6) Our program is evaluated on a continual basis. We propose to continue this successful program by requesting an increased level of support for six masters degree students over the next three-year period. The Graduate School and individual doctoral granting departments at UNC-Chapel Hill will provide matching funds to promote the success of the program.

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SES-0548858
Henry Frierson
University of North Carolina at Chapel Hill

SES-0549031
Robert Schwab
University of Maryland, College Park

SES- 0548909
Steven Ullmann
University of Miami

SES-0549057
Anne Donnelly
University of Florida

SES-0548986
Orlando Taylor
Howard University

The goal of the Atlantic Coast Social, Behavioral, and Economic Sciences (AC-SBE) Alliance, consisting of Howard University, the University of Florida, the University of Maryland at College Park, the University of Miami, and the University of North Carolina at Chapel Hill, is to increase the number of under-represented minority students receiving PhD degrees in the social, behavioral, and economic (SBE) sciences and ultimately entering the professoriate. All five universities are among the nation's leaders in awarding PhDs in the SBE fields to underrepresented minority students. The plan for the AC-SBE Alliance includes elements designed to help students at each step as they move from undergraduate school into graduate programs and onto the professoriate. The consortium has four objectives: (1) Recruit and prepare undergraduates to pursue a PhD in SBE fields, (2) Assist students in the transition from undergraduate to graduate study, (3) Retain PhD students and increase degree completion rates, and (4) Prepare future SBE faculty for success. Although each of the five schools in the AC-SBE alliance has unique features, the AC-SBE Alliance will include a number of overarching activities that will involve all five universities. For one example, the Alliance will build upon Howard University's Summer Institute that prepares future faculty in the STEM disciplines to launch a parallel SBE component. Also, entering AC-SBE students will be invited to participate in a one-week course Introduction to Data Analysis for the Social Sciences at the Odum Institute for Research in the Social Sciences at the University of North Carolina at Chapel Hill. The Odum Institute will also offer a number of videoconference short courses for AC-SBE students. Efforts will be made to ensure that the students in the SBE Alliance have further opportunities to interact and network at conferences such as the NSF-supported EMERGE.

Broader Impacts. Through integrating the resources of the five AC-SBE Alliance institutions, AC-SBE will have a broad impact across a wide region of the country in the eventual production of SBE PhD recipients. Thus, AC-SBE will serve as a comprehensive project for recruiting, mentoring, and graduating URM students in SBE PhD programs, and to carry out strategies to identify and broadly support URM students who want to pursue graduate studies and academic careers. The norms of inclusiveness at the AC-SBE Alliance institutions and the relationships that have been forged will endure well past the termination of grant support to continue efforts to ensure the significant numbers of minority students pursue and receive PhD degrees and enter the professoriate.

[unreadable] DESCRIPTION (provided by applicant): [unreadable] The program proposed here provides interdisciplinary, graduate training in areas related to drug and alcohol abuse. The objective of this program is the preparation of pre- and postdoctoral fellows for careers in basic or in more clinically-related research. Students are drawn from the Psychology Department and the Curriculum in Neurobiology at the University of North Carolina at Chapel Hill. Training sites include laboratories affiliated with the Experimental/Biological or the Clinical Psychology programs, the Curriculum in Neurobiology, the Center for Alcohol Studies, the School of Pharmacy, and the School of Social Work. The environment offered by UNC at Chapel Hill is particularly well-suited for training in research related to drug abuse. First of all, the faculty includes a core of individuals whose research and teaching activities provide a broad spectrum of high quality research training opportunities. These include behavioral pharmacology of drugs of abuse, neurobiolgy of opioid and dopamine systems, neuropharmocolgy of ethanol and other drugs of abuse, investigations of the immune system and drugs of abuse and clinically-related areas such as the progression of adolescent substance abuse and investigations of predictive risk factors. Secondly, interaction among investigators provides a strong collaborative environment for training students. Students receive background training either in the basic neural and behavioral sciences or the more clinically-oriented areas of psychology. More focused training related to drug abuse comes from a variety of interdepartmental courses and seminars and extensive laboratory research. Students who complete this program also receive training in teaching and communication, and are provided many opportunities to develop their professional leadership skills. Upon completion of their training, students are prepared to pursue a career related to drug abuse in academic, research, or clinical settings. [unreadable] [unreadable] [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): Seeding Postdoctoral Innovators in Research and Education (SPIRE) is an innovative post-doc training program that provides training experiences essential for success of the future's biomedical researchers. By merging research training with professional development emphasizing learning, education and communication, UNC Chapel Hill, in alliance with 7 NC historically minority universities (HMUs), via the Partnership for Minority Advancement in the Biomolecular Sciences (PMABS), has during the first SPIRE grant created a uniquely innovative program for post-docs that provides comprehensive training. This training develops research excellence, as well as learning/education excellence, which concurrently contributes to providing HMU minority students equal access to the knowledge and technology revolutions and opportunities with the goal of contributing to achieving diversity in biomedical careers. Integrated with other PMABS initiatives, SPIRE is a cogent example of the synergies that can be created between programs to open doors for trainees to novel, critically needed career paths - e.g., research, teaching, policy, ELSI-- that address the science crisis confronting this nation. This competing continuation renewal will advance SPIRE to the next significant level of excellence that will compellingly demonstrate the importance of providing new kinds of training to today's and tomorrow's researchers. Programmatic integration and innovation documented with tangible outcomes (e.g., success of post-docs and HMU minority students in biomedical careers), built upon evaluation and lessons learned/successes to date, will expand and refine SPIRE's well conceived original design in a variety of ways, including: 1) increase number of uniquely trained post-docs to meet burgeoning profession and HMU need; 2) diffuse IT innovation broadly to further advance post-doc and student success; 3) expand participation to include outstanding researchers from Duke University and NC State University; 4) target disciplines (e.g., genomics, bioinformatics, molecular genetics) to meet the urgent learning needs of HMU students; and 5) expand the exceptional opportunity for sustained post-doc mentoring of minority student research and thus advancement into research careers. SPIRE is poised to begin the needed revolution in post-doc traininq and diversity which will revitalize US born student interest in biomedical careers. [unreadable] [unreadable]

SES-0750385
Henry Frierson
Anne Donnelly
Carolyn Tucker
University of Florida

SES-0750663
Kim Nickerson
Johnetta Davis
Robert Schwab
University of Maryland, College Park

SES-0750657
Steven Ullmann
University of Miami

SES-0549057
Anne Donnelly
University of Florida

SES-0750683
Orlando Taylor
Florence Bonner
Angela Cole
Howard University

The grant provides three years of continued support to the Atlantic Coast Social, Behavioral, and Economic Sciences (AC-SBE) Alliance. AC-SBE, comprised of Howard University, University of Florida (lead institution), University of Maryland at College Park, University of Miami, and University of North Carolina at Chapel Hill, to complete a range of activities with the goal of increasing the number of under-represented minority students receiving doctorate degrees in the social, behavioral, and economic (SBE) sciences and ultimately entering the professoriate. All five universities are currently among the nation's leaders in awarding PhDs in the SBE fields to underrepresented minority students. The AC-SBE Alliance includes elements designed to help students at each step as they move from undergraduate school into graduate programs and onto the professoriate. The Alliance will continue to: (1) recruit and prepare undergraduates to pursue a PhD in SBE fields, (2) assist students in the transition from undergraduate to graduate study, (3) retain PhD students and increase degree completion rates, and (4) prepare future SBE faculty for success. Although each of the five schools in the AC-SBE alliance has unique features, the AC-SBE Alliance includes a number of overarching or "value-added" activities that involve sharing resources across the five universities. For example, the Alliance builds upon Howard University's Summer Institute that prepares future faculty in the STEM (science, engineering and technology) fields, adding a parallel SBE component. Also, entering AC-SBE students participate in a one-week course--Introduction to Data Analysis for the Social Sciences--at the Odum Institute for Research in the Social Sciences at the University of North Carolina at Chapel Hill. The Odum Institute also offers a number of videoconference short courses to AC-SBE students.

Broader Impacts. Through integrating the resources of the five Alliance institutions, AC-SBE has the potential to realize a broad impact across a wide region of the country in the production of SBE PhD recipients. Thus, AC-SBE serves as a comprehensive project for recruiting, mentoring, and graduating underrepresented students in SBE PhD programs, and further to more broadly support students who want to pursue graduate studies and academic careers. It is anticipated that the norms of inclusiveness at the AC-SBE Alliance institutions and the relationships that have been forged will endure well past the termination of grant support to continue efforts to ensure the significant numbers of minority students pursue and receive PhD degrees and enter the professoriate.

DESCRIPTION (provided by applicant): Seeding Postdoctoral Innovators in Research and Education (SPIRE) is an integrative postdoctoral fellowship program that combines research training, professional development and hands-on teaching experience. The program involves a partnership between the University of North Carolina at Chapel Hill and five Minority Serving Institutions (MSIs) in North Carolina with large minority undergraduate populations, including Fayetteville State University, Johnson C. Smith University, North Carolina A&T State University, North Carolina Central University and the University of North Carolina at Pembroke. The objective of this program is 1) to prepare individuals for research/academic careers in the biomedical sciences and 2) to have a continuing impact on the MSIs through the exchange that takes place as the postdoctoral scholars develop teaching expertise and share their knowledge in the sciences with the faculty and students at the MSIs. The proposal put forward here builds upon the past successes of the SPIRE program and lessons learned over the last eight years. Based on a thorough evaluation of the SPIRE program, the program proposes to continue to provide cutting-edge research training for SPIRE scholars by drawing upon a large core of faculty at UNC Chapel Hill. Taken together, these faculty members provide a broad spectrum of high quality research training opportunities within their laboratories and reveal a commitment to train scholars to think creatively, collaborate effectively and operate across disciplinary boundaries. The SPIRE program also proposes to provide pedagogical training for the scholars through a range of interactions such as, 1) instruction from the UNC Chapel Hill Center for Teaching and Learning and other education professionals, 2) technology workshops, and 3) creating opportunities for the scholars to practice active learning techniques and develop, individual advanced-level courses at the MSIs. Through these extensive teaching activities, the IRACDA scholars will introduce new, revised, and advanced courses at the MSIs and work closely with the undergraduates at these institutions, providing active learning experiences and close, individualized research mentoring. The SPIRE program also proposes to provide other professional development training in order to prepare scholars for careers that combine research and education. Professional development training includes numerous opportunities to make research presentations, to take part in the organization of an annual research symposium, and an annual distinguished scholar seminar, and attendance at monthly meetings with a professional focus. In addition, the scholars will receive training in grantsmanship through an in-house grant competition that requires each IRACDA scholar to prepare a research proposal and have it evaluated by a faculty committee. Taken together, these initiatives will provide the scholars with the skills required to function as independent researchers, research-oriented teachers and committed mentors for undergraduate students in the sciences. In the process, the MSIs will enjoy continued benefit through long-term modifications in curriculum and infrastructure. The diversity of the science community will be expanded by the enhanced interest in science careers among the undergraduate students at the MSIs who have been exposed to a vibrant, active learning experience.

DESCRIPTION (provided by applicant): The program proposed here is a continuation of an interdisciplinary, predoctoral training program in research related to drug abuse. The objective of this program continues to be the preparation of individuals for research, professional and teaching careers focused on drug abuse. Students are drawn from the Behavioral Neuroscience Program within the Department of Psychology or the Curriculum in Neurobiology at the University of North Carolina at Chapel Hill. The environment offered by UNC/Chapel Hill Is particularly well suited for training in research related to drug abuse. First of all, the faculty includes a core of individuals whose research and teaching activities provide a broad spectrum of high-quality, research training opportunities. These include the neurobiology of dopamine and opioid systems, the neuropharmacology of ethanol and other drugs of abuse, investigations of the immune system and drugs of abuse, behavioral genetics of drugs of abuse, and the behavioral, neurobiological and endocrine effects of cocaine and other psychomotor stimulants. Secondly, the interaction among investigators provides a strong collaborative environment for training students. All trainees receive formal training in the basic neural and behavioral sciences. More focused training related to drug abuse comes from a variety of interdepartmental courses and seminars and extensive laboratory research. Trainees also take part in conferences at national meetings, and receive training in teaching and communication. They participate in courses and discussions related to the ethical conduct of research, and are provided many opportunities to develop their professional leadership skills, including writing proposals and making formal presentations. Upon completion of their training, students are prepared to pursue a career related to drug abuse in academic or research-intensive settings. PUBLIC HEALTH RELEVANCE: Drug abuse remains a pressing problem in this country and the interdisciplinary training program proposed here addresses that problem by preparing individuals with the skills necessary to advance knowledge of the behavioral, neurobiological and pharmacological effects of drugs of abuse This knowledge is central to the development of treatments for those who are dependent upon drugs of abuse and for the prevention of drug abuse in others.

DESCRIPTION (provided by applicant): Diversity is highly significant to our nation's future health, educational, scientific and research enterprise, yet, diversity in the biomedical and scientific workforce does not reflect the U.S. population. SPIRE (Seeding Postdoctoral Innovators in Research and Education) has established itself as an innovative postdoctoral research and career development training program whose goals are aligned with those of IRACDA: 1) to inspire and motivate undergraduate students from underrepresented groups to engage in science-based course content, research, and to pursue graduate degrees in science while 2) providing training in research, teaching, and career development that promotes success of scholars in their own career goals. The underlying hypothesis of SPIRE is that faculty who combine excellence in research and teaching, and value the importance of mentoring and diversity, will effectively train the next generation of scientists and promote diversity in the scientific workforce. In response to SPIRE's ongoing evaluation, the current proposal maintains many successful components while also introducing several innovations to benefit our partner universities and our scholars. This proposal will support 30 new scholars over the duration of 5 years and partner with four universities, each with an historical commitment to train students from underrepresented groups. Specific Aims of the SPIRE program are to: 1. Recruit outstanding and diverse SPIRE scholars who represent the scientific mission of NIGMS and the education and research needs of our partner campuses. 2. Provide an outstanding research training experience by placing scholars in productive laboratories with mentors committed to the goals of SPIRE and ensuring that this research experience involves mentoring of undergraduates from our partner campuses. 3. Provide a mentored teaching experience at our partner campuses. This experience includes research-based courses and direct involvement with research initiatives at our partner campuses. 4. Provide training in professional skills that match the needs of our scholars and promote their success in attaining future positions in academia. Innovations in this proposed renewal include a) a new emphasis on recruiting SPIRE scholars with chemistry, physics and biomedical engineering backgrounds to meet the needs of our partner campuses; b) structured involvement with RISE and MARC programs at our partner campuses, including a summer research program at UNC/Chapel Hill for undergraduates from our partner campuses, c) new evaluation measures to track more effectively undergraduate student outcomes and d) mechanisms to facilitate the sharing of data and effective teaching strategies among current and former SPIRE scholars and faculty at our partner campuses. Impact: We aim to continue and enhance our documented and significant impact on the curriculum and research enterprise of our partner universities, and on the training of new faculty who are successful in research and science education as well as in promoting the diversity of our future scientific workforce. PUBLIC HEALTH RELEVANCE: The proportion of advanced degrees awarded to underrepresented groups in the biomedical and STEM disciplines continues to be very small and does not reflect the current demographics in the US. To address this shortage, the SPIRE/IRACDA program provides training in both research and teaching that prepares postdoctoral scholars to inspire and promote increased representation of underrepresented groups in the scientific work force.