PPG investigators are studying numerous genes and their protein products in the brain's reward circuits to define their role in drug abuse and addiction. To accomplish this goal, the Behavioral Core has established a broad battery of behavioral tests in rats and mice. This battery includes relatively routine, high throughput tests, including assays of locomotor activity and sensitization, conditioned place preference and aversion, opiate withdrawal, analgesia, and sucrose preference, to name a few. In addition, several more complex paradigms are available in the Core, such as the 5-choice serial reaction time test and other cognitive assays, as well as operant responding for food or sucrose. Conditioned reward and intracranial self-stimulation assays are made available to Project investigators via outside subcontracts. Core personnel will continually work to extend this battery to additional tests in the years ahead. The imperative to employ such a large battery of behavioral tests is that it is difficult to infer something about complex behavior from a single test or even a limited number of tests. Rather, by utilizing numerous complementary measures we are able to infer, with much greater accuracy, the role of a given gene in complex behavior related to addiction. By consolidating these behavioral tests within a centralized Core, we ensure rigorous control over the data as well as facilitate comparisons and contrasts of experimental results from the individual Projects. This consolidation also makes financial sense, since we can concentrate and maximize efficient use of our behavioral expertise. The role of specific target genes and proteins in behavioral responses related to drug abuse and addiction is tested with a variety of experimental approaches, including advanced mouse mutagenesis and viral gene transfer in conjunction with the Transgenic Core. We utilize: 1) intracerebral injections of specific activators or inhibitors of a target protein;2) intracerebral injections of viral vectors that overexpress the target protein itself or a dominant negative or other mutants of the protein;and 3) mutant mice that lack or overexpress the target protein or a dominant negative mutant. The latter includes mutant mice in which the target gene is overexpressed or knocked out in an inducible manner and selectively within a brain region of interest. The Behavioral Core then provides routine, high throughput behavioral tests for investigators in the individual Projects. Encouraging findings are pursued with the more sophisticated behavioral tests also available in the Core and with drug self-administration and relapse assays in conjunction with Project 4. Finally, the Core obtains routine plasma drug levels or related measurements (e.g., plasma corticosterone, electrolyte levels) in behaving animals as needed for particular experiments.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Program Projects (P01)
Project #
3P01DA008227-21S1
Application #
8684706
Study Section
Special Emphasis Panel (ZDA1-RXL-E)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2013-12-30
Support Year
21
Fiscal Year
2013
Total Cost
$139,577
Indirect Cost
$49,543
Name
Icahn School of Medicine at Mount Sinai
Department
Type
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Steinberg, Elizabeth E; Christoffel, Daniel J; Deisseroth, Karl et al. (2015) Illuminating circuitry relevant to psychiatric disorders with optogenetics. Curr Opin Neurobiol 30:16-Sep
Walker, Deena M; Cates, Hannah M; Heller, Elizabeth A et al. (2015) Regulation of chromatin states by drugs of abuse. Curr Opin Neurobiol 30:112-21
Koo, Ja Wook; Lobo, Mary Kay; Chaudhury, Dipesh et al. (2014) Loss of BDNF signaling in D1R-expressing NAc neurons enhances morphine reward by reducing GABA inhibition. Neuropsychopharmacology 39:2646-53
Peña, Catherine J; Bagot, Rosemary C; Labonté, Benoit et al. (2014) Epigenetic signaling in psychiatric disorders. J Mol Biol 426:3389-412
Heller, Elizabeth A; Cates, Hannah M; Peña, Catherine J et al. (2014) Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors. Nat Neurosci 17:1720-7
Maze, Ian; Chaudhury, Dipesh; Dietz, David M et al. (2014) G9a influences neuronal subtype specification in striatum. Nat Neurosci 17:533-9
Maze, Ian; Shen, Li; Zhang, Bin et al. (2014) Analytical tools and current challenges in the modern era of neuroepigenomics. Nat Neurosci 17:1476-90
Arango-Lievano, Margarita; Schwarz, Justin T; Vernov, Mary et al. (2014) Cell-type specific expression of p11 controls cocaine reward. Biol Psychiatry 76:794-801
Feyder, Michael; Södersten, Erik; Santini, Emanuela et al. (2014) A Role for Mitogen- and Stress-Activated Kinase 1 in L-DOPA-Induced Dyskinesia and ?FosB Expression. Biol Psychiatry :
Dong, Yan; Nestler, Eric J (2014) The neural rejuvenation hypothesis of cocaine addiction. Trends Pharmacol Sci 35:374-83

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