The objective of this Program Project Grant is to study the molecular neurobiological mechanisms underlying opiate and cocaine addiction. The program of research contains two major strengths. First, is the multidisciplinary nature of our ongoing and proposed research. Each research area represents an integration of molecular, biochemical, electrophysiological, neuropharmacological, and behavioral levels of analysis aimed at our basic research with a well-established clinical research program in drug abuse in our research group. The Program Project Grant is organized into a small Administrative Core, two scientific Cores, and five Projects. The transgenic Core is responsible for the breeding of may types of transgenic and knock out mice, and constructs for viral-mediated gene transfer, to be utilized in the proposed research. The Core is also responsible for the construction of several new lines of mutant mice, including those with inducible tissue-specific transgenes. The Behavioral Core is responsible for analysis of relatively routine drug-relative behaviors, including opiate withdrawal, locomotor activity, and place conditioning, in both rats and mice. Project 1 is a continuation of a productive and collaborative effort among several laboratories to study the molecular and cellular mechanisms by which opiates regulate locus coeruleus neurons and to relate these changes to behavioral measures of opiate withdrawal. Project 2 is a continuation of related collaborative studies that focus on molecular and cellular actions on opiates and cocaine in several other target brain regions, including dorsal raphe, prefrontal cortex, and lateral septum. Project 3 is a continuation of collaborative molecular, cellular, and behavioral studies of the role of specific neuropeptide receptors in the long-term actions of opiates and cocaine on specific target brain regions. Project 4 is a continuation of efforts to study the functional role by known molecular and cellular responses to drugs of abuse in the mesolimbic dopamine system. Animal models of drug reinforcement and craving, in conjunction with transgenic and viral-mediated gene transfer methods, will be used. Project 5 is a new effort to examine the genetic contributions to drug abuse in people. This work is an ideal way of applying fundamental knowledge arising from the basic Projects to clinical populations. Renewal of the Program Project Grant will enable continuation, and further strengthening, of our multidisciplinary research program into the molecular neurobiological mechanisms underlying drug addiction.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Program Projects (P01)
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Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Pollock, Jonathan D
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Yale University
Schools of Medicine
New Haven
United States
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Monteggia, Lisa M; Heimer, Hakon; Nestler, Eric J (2018) Meeting Report: Can We Make Animal Models of Human Mental Illness? Biol Psychiatry 84:542-545
Clark, Christopher R; Maile, Makayla; Blaney, Patrick et al. (2018) Transposon mutagenesis screen in mice identifies TM9SF2 as a novel colorectal cancer oncogene. Sci Rep 8:15327
Cates, Hannah M; Heller, Elizabeth A; Lardner, Casey K et al. (2018) Transcription Factor E2F3a in Nucleus Accumbens Affects Cocaine Action via Transcription and Alternative Splicing. Biol Psychiatry 84:167-179
Cahill, M E; Walker, D M; Gancarz, A M et al. (2018) The dendritic spine morphogenic effects of repeated cocaine use occur through the regulation of serum response factor signaling. Mol Psychiatry 23:1474-1486
Hamilton, Peter J; Burek, Dominika J; Lombroso, Sonia I et al. (2018) Cell-Type-Specific Epigenetic Editing at the Fosb Gene Controls Susceptibility to Social Defeat Stress. Neuropsychopharmacology 43:272-284
Egervari, Gabor; Kozlenkov, Alexey; Dracheva, Stella et al. (2018) Molecular windows into the human brain for psychiatric disorders. Mol Psychiatry :
de la Fuente Revenga, Mario; Ibi, Daisuke; Saunders, Justin M et al. (2018) HDAC2-dependent Antipsychotic-like Effects of Chronic Treatment with the HDAC Inhibitor SAHA in Mice. Neuroscience 388:102-117
Anderson, Ethan M; Sun, Haosheng; Guzman, Daniel et al. (2018) Knockdown of the histone di-methyltransferase G9a in nucleus accumbens shell decreases cocaine self-administration, stress-induced reinstatement, and anxiety. Neuropsychopharmacology :
Hamilton, Peter J; Lim, Carissa J; Nestler, Eric J et al. (2018) Stereotaxic Surgery and Viral Delivery of Zinc-Finger Epigenetic Editing Tools in Rodent Brain. Methods Mol Biol 1867:229-238
Inquimbert, Perrine; Moll, Martin; Latremoliere, Alban et al. (2018) NMDA Receptor Activation Underlies the Loss of Spinal Dorsal Horn Neurons and the Transition to Persistent Pain after Peripheral Nerve Injury. Cell Rep 23:2678-2689

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