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Brain imaging in nicotine addiction

Institution: University of California, Los Angeles
Investigator(s): Desmond Smith, Ph.D.
Award Cycle: 2002 (Cycle 11) Grant #: 11RT-0172 Award: $419,881
Subject Area: Nicotine Dependence
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Nicotine is one of the most profoundly addicting drugs known. If it were possible to design a drug that could break the vicious cycle of nicotine dependence, enormous numbers of lives would be saved by allowing people to give up smoking. Part of the difficulty in designing such drugs is the fact that we know very little about the molecules in the brain that are responsible for nicotine addiction. To better understand the genetic changes that occur in the brain as a result of addiction to nicotine, we have devised a new method called "voxelation". This technology combines rapid gene expression techniques with the mathematical foundations of CT and PET scanning. It is as if, instead of just one type of X-ray, there were thousands of different "types" of X-ray beam, each beam capable of tracking a different gene and providing a vivid 3D image of its expression pattern. Experiments are described that use the voxelation technology to identify the genetic changes that occur in the mouse brain as a result of chronic exposure to nicotine. These investigations should give a better understanding of the genetic networks responsible for nicotine addiction. In the longer term, the significance in nicotine addiction of the genes uncovered by voxelation can be tested in living mice by using genetic engineering and behavioral studies. Genes identified as playing an important role in nicotine dependence by these investigations will be very attractive targets for the development of new drugs to cure smokers of their nicotine addiction.
Publications

Genes regulated by learning in the hippocampus.
Periodical: Journal of Neuroscience Research Index Medicus:
Authors: Leil TA, Ossadtchi A, Nichols TE, Leahy RM, Smith DJ ART
Yr: 2003 Vol: 71 Nbr: Abs: Pg: 763-768

Error-correcting microarray design.
Periodical: Genomics Index Medicus:
Authors: Khan AH, Ossadtchi A, Leahy RM, Smith DJ ART
Yr: 2003 Vol: 81 Nbr: Abs: Pg: 157-165

High-resolution voxelation mapping of human and rodent brain gene expression.
Periodical: Journal of Neuroscience Methods Index Medicus:
Authors: Singh RP, Brown VM, Chaudhari A, Khan AH, Ossadtchi A, Sforza DM, Smith DJ, et al ART
Yr: 2003 Vol: 125 Nbr: Abs: Pg: 93-101

Genome scale three dimensional brain gene expression mapping in the mammalian brain.
Periodical: Psychiatric Research Soc Index Medicus:
Authors: Brown VM, Ossadtchi A, Khan AH, Yee S, Lacan G, Melega WP, Cherry SR, Leahy RM, Smith DJ ABS
Yr: 2003 Vol: Nbr: Abs: Pg:

Identifying loci for behavioral traits using genome-tagged mice.
Periodical: Journal of Neuroscience Research Index Medicus:
Authors: Liu D, Singh RP, Khan AH, Bhavsar K, Lusis AJ, Davis RC, Smith DJ ART
Yr: 2003 Vol: 74 Nbr: Abs: Pg: 562-569

Genome scale mapping of brain gene expression.
Periodical: Biological Psychiatry Index Medicus:
Authors: Singh RP, Smith DJ ART
Yr: 2003 Vol: 53 Nbr: Abs: Pg: 1069-1074

Genetic and genomic strategies in learning and memory.
Periodical: Current Genomics Index Medicus:
Authors: Sforza DM, Smith DJ ART
Yr: 2003 Vol: 4 Nbr: Abs: Pg: 475-485

Voxelation and gene expression tomography for the acquisition of 3-D gene expression maps in the brain.
Periodical: Methods Index Medicus:
Authors: Liu D, Smith DJ ART
Yr: 2003 Vol: 31 Nbr: Abs: Pg: 317-325

Anatomical methods for voxelation of the mammalian Brain.
Periodical: Neurochemistry Research Index Medicus:
Authors: Sforza DM, Annese J, Liu DH, Levy S, Toga AW, Smith DJ ART
Yr: 2004 Vol: 29 Nbr: Abs: Pg: 1299-1306

Multi-fluorophore spectral deconvolution with a hyperspectral imaging apparatus.
Periodical: Society Molecular Imaging Index Medicus:
Authors: Zavattini G, Vecchi S, Leahy RM, Smith DJ, Cherry SR ABS
Yr: 2003 Vol: Nbr: Abs: Pg:

Genome-scale mapping of brain gene expression patterns.
Periodical: Society Molecular Imaging Index Medicus:
Authors: Smith DJ, Singh RP, Brown VM, Ossadtchi A, Chaudhari A, Khan AH, Sforza DM, et al ABS
Yr: 2003 Vol: Nbr: Abs: Pg:

Hyperspectral optical fluorescence tomography for small animal imaging.
Periodical: Society Molecular Imaging Index Medicus:
Authors: Chaudhari A, Darvas F, Serrano N, Smith DJ, Cherry SR, Leahy RM ABS
Yr: 2003 Vol: Nbr: Abs: Pg:

Functional analysis of genes implication in Down Syndrome, Cognitive abilities in transpolygenic mice for down syndrome chromosomal region (DCR-1)
Periodical: Behav Genet Index Medicus:
Authors: Chabert C, Jamon M, Cherfouh A, Duquenne V, Smith DJ, ART
Yr: 2004 Vol: 34 Nbr: Abs: Pg: 559 - 569

Investigation of different transcript quantitation tools for voxelation.
Periodical: Journal Molecular Histol Index Medicus:
Authors: Singh RP, Liu D, Chaudhari A, Leahy RM, Smith DJ ART
Yr: 2004 Vol: 35 Nbr: Abs: Pg: 397 - 402

Functional analysis of genes implicated in down syndrome: 2 laterality and corpus callosum size in mice transpolygenic for down syndrome chromosomal region-1 (DCR-1)
Periodical: Behav Genet Index Medicus:
Authors: Roubertoux PL, Smith DJ, Bichler Z, Pinoteau W, Seregaza Z, Fortes S, et al ART
Yr: 2005 Vol: 35 Nbr: Abs: Pg: 333 - 341

Voxelation methods for genome scale imaging of brain gene expression.
Periodical: Meth Enzymol Index Medicus:
Authors: Sforza DM, Smith DJ ART
Yr: 2004 Vol: 386 Nbr: Abs: Pg: 314 - 323

A genome-wide set of congenic mouse strains derived from DBA/23 on a C57BL/6J background.
Periodical: Genomics Index Medicus:
Authors: Smith DJ, Davis RC, Schadt EE, Hsieh EWY, Cervino ACL, et al ART
Yr: 0 Vol: Nbr: Abs: Pg: