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					Division of Basic Neuroscience
   and Behavioral Research
           (DBNBR)


       David Shurtleff, Ph.D.
             Director

      Research Training Director’s Meeting
              November 3, 2006
           DBNBR Goals

Identify antecedents and consequences of
drug abuse and addiction
Develop and exploit new technologies,
models, paradigms
Identify genetic & developmental
vulnerabilities for drug abuse
Foster transdisciplinary/integrative research
and training
Division of Basic Neuroscience and Behavioral Research

 Technology                        Office of the Director                          Training
Development                 David Shurtleff, PhD - Director                  Charles Sharp, PhD
                            Paul Schnur, PhD - Deputy Director                     Special Assistant &
Karen Skinner, PhD          Joni Rutter, PhD- Assoc Director Population
 Deputy Director                                                                   Training Coordinator
                                                & Applied Genetics           Beth Babecki, MA
 for Science and            Christie Baxter, BA – Program Analyst
   Technology                                                                      Deputy Training
                            Amira Debbas, BA – Program Analyst                     Coordinator
   Development              Joyce Williams – Program Analyst                 Diane Lawrence, PhD



Behavioral and Cognitive                               Chemistry and Physiological
Science Research Branch                                 Systems Research Branch
       Minda Lynch, PhD, Chief                                   Rao Rapaka ,PhD, Chief
            Tom Aigner, PhD                                         Paul Hillery, PhD
        Allison Chausmer, PhD                                        Kevin Gormley
         Susan Volman, PhD                                          Hari Singh, PhD
     Cora Lee Wetherington, PhD                                   Pushpa Thadani, PhD
    (Women’s Health Coordinator)                                   Dave Thomas, PhD




 Functional Neuroscience                                    Genetics and Molecular
    Research Branch                                      Neurobiology Research Branch
       Nancy Pilotte, PhD, Chief                                Jonathan Pollock, PhD, Chief
       Jerry Frankenheim, PhD                                      Christine Colvis, PhD
        Diane Lawrence, PhD                                         John Satterlee, PhD
          Geraline Lin, PhD                                           Da Yu Wu, PhD
         Yu (Woody) Lin, PhD
Drug Addiction: A Complex Behavioral and
        Neurobiological Disorder
   HISTORY                                      BIOLOGY
   - previous history     DRUGS                 - genetics
                                                - circadian rhythms
   - expectation
   - learning                                   - disease states
                                                - gender




                      BRAIN
                    MECHANISMS


                        ADDICTION


                   ENVIRONMENT
                        - social interactions
                        - stress
                        - conditioned stimuli
 Repeated Drug Abuse Increases Genetic Transcription
     Resulting in Long-term Structural Changes




                                   Dopamine




             Dendritic
              Spines




Adapted from Nestler E.J.
Science & Practice Perspectives,
5(1) 2005.
 Chronic cocaine increases density of dendritic spines and
      neuronal branching in the nucleus accumbens



      11                                                             60



      10                                                             55




                                                          Branches
                                                                                    COC


       9                                                             50


                                                                                    CTL
       8                                                             45
               CTL       COC             CTL        COC                   CTL COC


Robinson, T.E. & Kolb, B. Eur. J. of Neuro. 1999.
Ferrario, C.R. et al. Biol. Psychiatry, 2005.
                              Drug Addiction is a Developmental Disease with High
                                           Prevalence in Adolescence
Percentage in each age group who develop




                                           1.8%
                                                  TOBACCO
                                           1.6%
                                                                     THC
                                           1.4%
                                                                        ALCOHOL
                                           1.2%
  first time dependence




                                           1.0%

                                           0.8%

                                           0.6%

                                           0.4%

                                           0.2%
       -




                                           0.0%
                                                  5 10 15 21 25 30 35 40 45 50 55 60 65
                                                                          Age

                                            NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003
                                                Highly Rewarding Effect of Nicotine/Acetaldehyde
                                                              During Adolescence
   Mean Self-Injections (Nose-pokes in 3 hr)




                                               40       Nic/Acet 30/16 µg (N=11)                   Nic/Acet 30/16 µg (N = 6)    P90 Males
                                                                                   P27 Males
                                                        Acet 16 µg (N = 8)                         Acet 16 µg (N = 6)
                                                        Nic 30 µg (N=9)            **              Nic 30 µg (N = 10)
                                                        Saline 100 µl (N=7)
                                                                           **            **        Saline µg (N = 8)
                                               30                **


                                               20       *


                                               10




                                               0
                                                    0   1         2         3      4     5     0    1          2           3    4      5

                                                                       Test Day                                      Test Day

Belluzzi, et al., Neuropsychopharmacology, 2005 Apr;30(4):705-12.
    Drug Addiction Is Influenced by
Interactions of Genes and Environment


                             Twin studies
                        consistently show that
                          there is a heritable
                          component to drug
                         abuse and addiction.

                        What are the gene variants?


                   Intramural Study        Extramural Study
                         NIDA           NIDA/Perlegen/WashU
               Affymetrix 500K screen    Whole Genome Scan
                  for Drug Addiction     for Nicotine Addiction
    Many of These Genes Have Synaptic Functions

    presynaptic
        CELL


                         {
    ADHESION

  NEURO-
TRANSMISSION
       Dendritic
   SIGNAL
        Spines
TRANSDUCTION



                         {
  postsynaptic
TRANSCRIPTION
   FACTORS
De Camilli et al, 2001




                             Dean and Dresbach, TINS, 2006
       Functional Genomics
Need: Functional validation of gene
variant                                           Genome-wide
                                                   association
Capitalize on:                                        scans
   NIH Knockout Mouse Project
   High-throughput genetic and RNAi methods
   Research in GEI (FY11&12)                          Gene
                                                     variants
Use genetic models to:
   Investigate mechanisms of drug
   dependence
                                              What is the functional
   Test potential therapeutics                   significance?
        Addiction is a Complex Behavioral,
       Neurobiological, and Genetic Disorder


ENVIRONMENT & DRUG   GENETIC    SYNAPTIC      BRAIN
     EXPOSURE        VARIANTS   PLASTICITY   CHANGES
DBNBR Research Training
Framework to enhance cooperative activities among 16 NIH
Institutes and Centers

Take on challenges in neuroscience that are best met collectively
Develop research tools and infrastructure that will serve the entire
neuroscience community
Research Training Programs
    Training in Neuroscience Imaging (Steve Grant, PO)
    Computational Neuroscience (Susan Volman, PO)
    Neurobiology of Disease (Beth Babecki, PO)
    Jointly Sponsored Predoctoral Program in the Neurosciences (JSPTPN)
    (Beth Babecki, PO)
      NIH Roadmap FOR Medical Research



    TransNIH initiative for a more efficient and productive system of medical
    research

    Identifies themes in three main areas for support:
          New pathways to discovery
          Research teams of the future
          Re-engineering the clinical research enterprise

•   NIDA lead on Interdisciplinary Research Training initiative
      –   Support didactic and research experiences designed to provide students
          with the knowledge and research experiences necessary to develop
          interdisciplinary solutions
      –   Allison Chausmer (lead program officer)
        Career Development Plan
           Pre-Doctoral            Institutional Pre-Doctoral
                       *
          Fellowship-F31                 Fellowship-T32




          Post-Doctoral             Institutional Post-Doctoral
                       *
          Fellowship-F32                   Fellowship-T32



        Do I need more training or changing career emphasis?      *
        Yes                                   No
    Apply for Mentored K            Do I have pilot data?

                                  Yes                   No
                                          Apply for R03,
                           R01            BSTART or ISTART
* Contact Program
Mentored Career Development Awards

    Mentored Research Scientist Development
    Award (K01)
    NIH Pathway to Independence (PI) Award
    (K99/R00)
    Mentored Clinical Scientist Development
    Award (K08)
    Mentored Quantitative Research Career
    Development Award (K25)
    Mentored Patient-Oriented Research Career
    Development Award (K23)
Progress Review of T32s
Trainee progress (publications, placement, mentors)
Program features and changes (breadth, student
diversity, scientific diversity)
Interactions
   Scientific
   Career development

Use of slots (level, length, throughput, transition to
independence)
Contingency planning for gaps in funding (last year of
T32)- Looking beyond supplements
Enhancing the Training Experience
 Scientific Meetings
      NIDA/SfN Mini-convention
          Poster presentation
          Travel awards

 Networking
      CPDD/ INRC/ SNIP etc. training mixers
      NIDA/SfN Mini-convention/NIDA exhibit

 Grantsmanship
      CPDD Grant writing workshop/tutorial
      SFN NIH Professional “Survival” Skills Workshop
 NIDA-supported Scientific Training
      Cold Spring Harbor
      Summer Institute
      Woods Hole
DBNBR Training Coordinators



             Charles Sharp: csharp1@nida.nih.gov
              301-443-1887

            Beth Babecki:
               - -           bbabecki@nida.nih.gov
              301-443-1887

            Diane Lawrence: LawrenceDi@nida.nih.gov
              301-443-1887

				
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