The personal, social and criminal ramifications of psychostimulant abuse is an enormous problem in North America. Clarifying the neural substrates that underlie addiction to drugs of abuse is critical for designing rational pharmacological interventions with the potential to cure addicts. A point in the cycle of addiction where pharmacological intervention can be particularly beneficial is to interfere with the overwhelming desire by addicts to use drugs. The Neurobiology of Addiction Research Center (NARC) uses a rat model of cocaine-seeking and unites an assemblage of investigators with expertise in behavior, neurochemistry, electrophysiology and cell biology. An Animal Core will generate rats with a history of stable cocaine self-administration that have been withdrawn from drug in an extinction or abstinence paradigm. After withdrawal, cocaine-seeking will be induced by presentation of conditioned cues, cocaine or drug context. The rats are then dispersed to the various projects for neurobiological evaluations. This core facility will insure consistency in experimental subjects, thereby permitting more accurate associations to be made between neuroadaptations associated with cocaine-seeking. Another aspect of the NARC that will be held constant is examining the same limbic-motor circuit. Project 1 endeavors to link changes in synaptic proteins, dendritic morphology and electrophysiology in excitatory accumbens synapses that are associated with cocaine-seeking. As well, project 1 will evaluate behaviorally effective medications for effects on the cocaine associated neuroplasticity. Project 2 will explore the cellular basis underlying the capacity of prefrontal BDNF administration to ameliorate cocaine-seeking, with a focus on prefrontal output to the nucleus accumbens and ventral tegmental area. Project 3 explores the neurobiological mechanisms whereby orexin antagonists inhibit cocaine-seeking, focusing on projections to the ventral tegmental area and prefrontal cortex. Finally, Project 4 will examine novel treatments derived from the first 3 projects that possess potential for inhibiting drug-seeking behavior. Thus, this project acts as a translational program to identify systemically active compounds with the potential for entering clinical trials. In addition to this highly integrated, multi-disciplinary approach to the neurobiology and treatment of cocaine-seeking, the NARC will facilitate scientific interactions, provide oversight and mentor junior faculty, pre- and postdoctoral trainees and undergraduates. In part this will be accomplished through a Pilot Core that will directly involve young and established investigators outside the field of addiction in evaluating novel hypotheses related to the neurobiology of relapse. In summary, the NARC provides a multidisciplinary research assault on the neurobiology and medications development for cocaine-seeking and is a mechanism for actively mentoring faculty and trainees. CENTER CHARACTERISITICS

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
3P50DA015369-07S2
Application #
7847093
Study Section
Special Emphasis Panel (ZDA1-RXL-E (02))
Program Officer
Frankenheim, Jerry
Project Start
2003-08-01
Project End
2011-10-31
Budget Start
2009-06-20
Budget End
2011-10-31
Support Year
7
Fiscal Year
2009
Total Cost
$75,638
Indirect Cost
Name
Medical University of South Carolina
Department
Neurosciences
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Spencer, Sade; Neuhofer, Daniela; Chioma, Vivian C et al. (2018) A Model of ?9-Tetrahydrocannabinol Self-administration and Reinstatement That Alters Synaptic Plasticity in Nucleus Accumbens. Biol Psychiatry 84:601-610
Parrilla-Carrero, Jeffrey; Buchta, William C; Goswamee, Priyodarshan et al. (2018) Restoration of Kv7 Channel-Mediated Inhibition Reduces Cued-Reinstatement of Cocaine Seeking. J Neurosci 38:4212-4229
Kearney-Ramos, Tonisha E; Lench, Daniel H; Hoffman, Michaela et al. (2018) Gray and white matter integrity influence TMS signal propagation: a multimodal evaluation in cocaine-dependent individuals. Sci Rep 8:3253
Giannotti, Giuseppe; Barry, Sarah M; Siemsen, Ben M et al. (2018) Divergent Prelimbic Cortical Pathways Interact with BDNF to Regulate Cocaine-seeking. J Neurosci 38:8956-8966
Siemsen, Ben M; Lombroso, Paul J; McGinty, Jacqueline F (2018) Intra-prelimbic cortical inhibition of striatal-enriched tyrosine phosphatase suppresses cocaine seeking in rats. Addict Biol 23:219-229
Hanlon, Colleen A; Dowdle, Logan T; Gibson, Nicole B et al. (2018) Cortical substrates of cue-reactivity in multiple substance dependent populations: transdiagnostic relevance of the medial prefrontal cortex. Transl Psychiatry 8:186
Roberts-Wolfe, Douglas; Bobadilla, Ana-Clara; Heinsbroek, Jasper A et al. (2018) Drug Refraining and Seeking Potentiate Synapses on Distinct Populations of Accumbens Medium Spiny Neurons. J Neurosci 38:7100-7107
Moorman, David E; James, Morgan H; Kilroy, Elisabeth A et al. (2017) Orexin/hypocretin-1 receptor antagonism reduces ethanol self-administration and reinstatement selectively in highly-motivated rats. Brain Res 1654:34-42
Bobadilla, Ana-Clara; Heinsbroek, Jasper A; Gipson, Cassandra D et al. (2017) Corticostriatal plasticity, neuronal ensembles, and regulation of drug-seeking behavior. Prog Brain Res 235:93-112
Barry, Sarah M; McGinty, Jacqueline F (2017) Role of Src Family Kinases in BDNF-Mediated Suppression of Cocaine-Seeking and Prevention of Cocaine-Induced ERK, GluN2A, and GluN2B Dephosphorylation in the Prelimbic Cortex. Neuropsychopharmacology 42:1972-1980

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