Abstract

The overall goal of this R01 and its companion IRPG proposals is to determine if there is altered dopamine neurotransmission in high risk nonalcoholics which predates the development of alcoholism and whether this dopaminergic defect is further deranged by chronic alcoholism. This R01 will examine dopamine release in chronic alcoholics and controls with PET scanning procedures and will relate this information to response to a Naloxone challenge. The investigators propose a model that alcoholism results from a deficiency of mesolimbic dopamine D2 receptors. An individual's low D2 receptor activity can be the result of genetic variance in the D2 receptor itself caused by the presence of the A1 D2 receptor allele, down regulation secondary to increased dopamine release secondary to stress-induced hypercortisolemia due to an anxious/depressed personality type or novelty seeking behavior, and the toxic effects of alcohol abuse per se. If the initial D2 receptor deficits are exacerbated by alcohol abuse one can envision a positive feedback loop hard to break.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA012839-03
Application #
6533644
Study Section
Alcohol and Toxicology Subcommittee 4 (ALTX)
Program Officer
Silverman, Peter
Project Start
2000-09-28
Project End
2005-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
3
Fiscal Year
2002
Total Cost
$741,752
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Robert Braši?, James; Mari, Zoltan; Lerner, Alicja et al. (2018) Remission of Gilles de la Tourette Syndrome after Heat-Induced Dehydration. Int J Phys Med Rehabil 6:
Rosenberg, Paul B; Wong, D F; Edell, S L et al. (2013) Cognition and amyloid load in Alzheimer disease imaged with florbetapir F 18(AV-45) positron emission tomography. Am J Geriatr Psychiatry 21:272-8
Rahmim, Arman; Zhou, Yun; Tang, Jing et al. (2012) Direct 4D parametric imaging for linearized models of reversibly binding PET tracers using generalized AB-EM reconstruction. Phys Med Biol 57:733-55
Lu, Lijun; Karakatsanis, Nicolas A; Tang, Jing et al. (2012) 3.5D dynamic PET image reconstruction incorporating kinetics-based clusters. Phys Med Biol 57:5035-55
Tang, Jing; Kuwabara, Hiroto; Wong, Dean F et al. (2010) Direct 4D reconstruction of parametric images incorporating anato-functional joint entropy. Phys Med Biol 55:4261-72
Steele, Kimberley E; Prokopowicz, Gregory P; Schweitzer, Michael A et al. (2010) Alterations of central dopamine receptors before and after gastric bypass surgery. Obes Surg 20:369-74
Wong, Dean F; Rosenberg, Paul B; Zhou, Yun et al. (2010) In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F 18). J Nucl Med 51:913-20
Zhou, Yun; Ye, Weiguo; Brasi?, James R et al. (2010) Multi-graphical analysis of dynamic PET. Neuroimage 49:2947-57
Zhou, Yun; Ye, Weiguo; Brasi?, James R et al. (2009) A consistent and efficient graphical analysis method to improve the quantification of reversible tracer binding in radioligand receptor dynamic PET studies. Neuroimage 44:661-70
Wong, Dean F; Tauscher, Johannes; Gründer, Gerhard (2009) The role of imaging in proof of concept for CNS drug discovery and development. Neuropsychopharmacology 34:187-203

Showing the most recent 10 out of 28 publications