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Transcript of NA shell NA shell vPFC mVP VTA NA core NA core dPFC SN dVP Blockade in these regions blocks relapse...
Science of Drug Addiction “In the past 30 years,
advances in science have revolutionized our understanding of drug abuse and addiction. We now know that drug addiction is a complex brain disease. It involves multiple factors and usually starts in adolescence.”Nora D. Volkow, M.D.
Director, National Institute on Drug Abuse
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Blockade in these regions blocks relapse or reinstatement
Drug Seeking Behavior – Motor Subcircuit
glutamate
Reward – Limbic Subcircuit
dopamine
Blockade in theseregions blocksinitiation of druguse, but notrelapse
Different Brain Circuitry Involved inDrug Reward and Drug Persistence Behavior
Different Brain Circuitry Involved inDrug Reward and Drug Persistence Behavior
Source: Adapted from McFarland, K. and Kalivas, P.W. Journal of Neuroscience, 21(21), pp. 8655-8663, November 1, 2001.Source: Adapted from McFarland, K. and Kalivas, P.W. Journal of Neuroscience, 21(21), pp. 8655-8663, November 1, 2001.
NIDA’s Neuroscience Program
Defining the Problems...Defining the Problems...
Developing the Tools...Developing the Tools...
Genetics Research at NIDAGenetics Research at NIDA
40-50% of the vulnerability to addiction is genetic
Genetic Variation Predicts Naltrexone Treatment Response for Alcohol Dependence
Genetic Variation Predicts Naltrexone Treatment Response for Alcohol Dependence
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Naltrexone/Asp40 Allele (A/G, G/G) (n=23)
Naltrexone/Asn40 Allele (A/A) (n=48)
Placebo/Asn40 Allele (A/A) (n=41)
Placebo/Asp40 Allele (A/G, G/G) (n=18)
Oslin, Berrettini, Volpicelli, Kranzler, O’Brien, et al., 2003Oslin, Berrettini, Volpicelli, Kranzler, O’Brien, et al., 2003
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AMPHAMPHAMPHAMPH DOIDOIDOIDOI
Amphetamine and the Hallucinogen DOI Amphetamine and the Hallucinogen DOI Produce Different Protein Profiles in Produce Different Protein Profiles in
BrainBrain
Amphetamine and the Hallucinogen DOI Amphetamine and the Hallucinogen DOI Produce Different Protein Profiles in Produce Different Protein Profiles in
BrainBrain
High-Throughput Genome-Wide Scan High-Throughput Genome-Wide Scan for Addiction Locifor Addiction Loci
High-Throughput Genome-Wide Scan High-Throughput Genome-Wide Scan for Addiction Locifor Addiction Loci
• NIDA plans to work with Perlegen Sciences to utilize their resource of 1.5 million single nucleotide polymorphisms in a whole genome scan to identify drug addiction loci
• Three groups from the NIDA Genetics Consortium competed for access to the Perlegen resource -- A group studying nicotine genetics, headed by Dr. Laura Bierut, has been granted access
• NIDA plans to work with Perlegen Sciences to utilize their resource of 1.5 million single nucleotide polymorphisms in a whole genome scan to identify drug addiction loci
• Three groups from the NIDA Genetics Consortium competed for access to the Perlegen resource -- A group studying nicotine genetics, headed by Dr. Laura Bierut, has been granted access
40-50% of the vulnerability to addiction is genetic
ADDICTION IS A DEVELOPMENTAL DISEASE It starts in adolescence and childhood
NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003
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Age at cannabis use disorder as per DSM IV
Copyright ©2004 by the National Academy of Sciences Gogtay, Giedd, et al. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-8179
Brain Maturation from Ages 5 to 20
Partial Recovery of Brain Metabolism and Function in Methamphetamine Abusers After
Protracted Abstinence
Partial Recovery of Brain Metabolism and Function in Methamphetamine Abusers After
Protracted Abstinence
Short AbstinenceShort Abstinence
Protracted AbstinenceProtracted Abstinence% Metabolic Change
Improved memory correlates with thalamic recovery
Improved memory correlates with thalamic recovery
Adapted from Wang, Volkow, et al, (2004) American Journal of Psychiatry 161: 242-8 (scans unpublished)
Genetics Mechanisms Treatments Genetics Mechanisms Treatments
We Are Using Science toDevelop Even Better Treatment
We Are Using Science toDevelop Even Better Treatment
NIDA Has Numerous Mechanisms To Fund Innovative
Drug Abuse Research
NIDA Has Numerous Mechanisms To Fund Innovative
Drug Abuse Research
Some Recent RFAs and PAsSome Recent RFAs and PAs RFA-DA-05-003RFA-DA-05-003 Developmental Centers for Translational Developmental Centers for Translational
Research on the Clinical Neurobiology of Drug AddictionResearch on the Clinical Neurobiology of Drug Addiction
PA-04-152PA-04-152 MDMA: Research Areas Needing More Interest MDMA: Research Areas Needing More Interest
PA-04-110PA-04-110 Prescription Drug Abuse Prescription Drug Abuse
PA-03-175PA-03-175 Fine Mapping Genes and Gene Variants for Drug Fine Mapping Genes and Gene Variants for Drug Addiction SusceptibilityAddiction Susceptibility
PA-03-155PA-03-155 Molecular Genetics of Drug Addiction Vulnerability Molecular Genetics of Drug Addiction Vulnerability
PAR-03-146PAR-03-146 (B/START) Behavioral Science Track Award for (B/START) Behavioral Science Track Award for Rapid TransitionRapid Transition
PAR-03-017PAR-03-017 Cutting-Edge Basic Research Awards (CEBRA) Cutting-Edge Basic Research Awards (CEBRA)
Find out more at: Find out more at: http://www.drugabuse.gov/funding/resfundslist.htmlhttp://www.drugabuse.gov/funding/resfundslist.html
NIDA CEBRA PROGRAMNIDA CEBRA PROGRAM
Foster highly innovative, novel or conceptually creative research that advances our understanding of drug abuse and addiction
Support research that is high-risk and potentially high-impact and that is underrepresented or not included in NIDA's current portfolio
PURPOSE
Micro-optical probesMicro-optical probes
CEBRA: Two-photon endoscopyCEBRA: Two-photon endoscopy(Mark Schnitzer)(Mark Schnitzer)
NIH ROADMAPNIH ROADMAPNIH ROADMAPNIH ROADMAP
• Building Blocks, Biological Pathways and Networks
• Molecular Library and Imaging
• Structural Biology• Nanomedicine• Bioinformatics and
Computational Biology
NEW PATHWAYS TO DISCOVERY
To accelerate the discovery and translation of biomedical research into new and effective prevention and treatment strategies.
RESEARCH TEAMS OF THE FUTURE• High-Risk Research• Interdisciplinary Research
RE-ENGINEERING THE CLINICAL RESEARCH ENTERPRISE
• Public-Private Partnerships
Current and Future Roadmap Funding OpportunitiesCurrent and Future Roadmap Funding Opportunities NEW PATHWAYS TO DISCOVERYMolecular Libraries and Imaging• Novel Preclinical Tools for Predictive ADME-
Toxicology • Cheminformatics Research Centers • Assay Technology Development (Re-
issuance)
• Pilot Scale Libraries for High Throughput Screening
• New Methodologies for Natural Products Chemistry
Building Blocks, Biological Pathways • National Technology Centers for Networks & Pathways (Re-issuance)Bioinformatics and Computational Biology• National Centers for Biomedical Computing (Re-issuance)Structural Biology• Membrane Protein Production and Structure DeterminationNanomedicine: Nanomedicine Development Centers
Neurosciences
Blueprint
Neurosciences
Blueprint
Sunday, October 24, 1:00 p.m.–3:00 p.m.Sunday, October 24, 1:00 p.m.–3:00 p.m.
Convention Center, Room 3Convention Center, Room 3
•Funding Opportunities:Funding Opportunities: http://www.drugabuse.gov/funding/resfundslist.html
•Training Opportunities:Training Opportunities: www.drugabuse.gov/researchtraining/traininghome.html
•Roadmap activities:Roadmap activities: http://www.drugabuse.gov/about/roadmap/index.html
www.drugabuse.govwww.drugabuse.gov