Alcohol abuse and alcoholism is a major public health problem in the United States, but little is known of the neurochemical pathways in the human brain that mediate the reinforcing and other properties of ethanol. The brain's endogenous opioid system is known to play an important role in reward mechanisms and recently it has been targeted in treatment efforts using the opiate antagonist naltrexone. The rationale for using opioid blockade in the treatment of alcoholism is well founded in experimental animal models of human alcohol use and abuse, but we know little about the underlying differences in the endogenous opioid system between healthy individuals and alcoholics. Positron emission tomography (PET) is a non-invasive imaging method that can be used to image and quantitate a number of neuromarkers and mu opioid receptors can be imaged in the human brain by PET using the well-validated ligand C-11 carfentanil. Our long-term goal is to better understand the function of the endogenous brain opioid system in alcohol use and abuse, and determine if it is involved in increasing the risk of alcoholism. The use of PET to measure regional mu opioid receptors is an approach that could provide new insight into the role of the endogenous opioid system in alcoholism.
The specific aims of this study are: l) Measure regional mu opioid receptor binding by PET in non-alcoholic men and women with a positive family history of alcoholism.; 2) Measure regional brain mu opioid receptor binding by PET in FHP and FHN alcoholic men and women and relate regional binding to behavioral measures of alcohol abuse; and 3) Measure the change in regional mu opioid receptor binding during one month controlled abstinence from ethanol in alcoholic men and women.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA011872-02
Application #
6168674
Study Section
Special Emphasis Panel (ZRG1-HPD (06))
Program Officer
Witt, Ellen
Project Start
1999-07-01
Project End
2003-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
2
Fiscal Year
2000
Total Cost
$478,133
Indirect Cost
Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Weerts, Elise M; Wand, Gary S; Kuwabara, Hiroto et al. (2014) Association of smoking with ?-opioid receptor availability before and during naltrexone blockade in alcohol-dependent subjects. Addict Biol 19:733-42
Weerts, Elise M; McCaul, Mary E; Kuwabara, Hiroto et al. (2013) Influence of OPRM1 Asn40Asp variant (A118G) on [11C]carfentanil binding potential: preliminary findings in human subjects. Int J Neuropsychopharmacol 16:47-53
Stephens, Mary Ann C; McCaul, Mary E; Weerts, Elise M et al. (2012) Serotonin transporter-linked polymorphic region (5-HTTLPR) genotype is associated with cortisol responsivity to naloxone challenge. Psychopharmacology (Berl) 224:223-30
Weerts, Elise M; Wand, Gary S; Kuwabara, Hiroto et al. (2011) Positron emission tomography imaging of mu- and delta-opioid receptor binding in alcohol-dependent and healthy control subjects. Alcohol Clin Exp Res 35:2162-73
Wand, Gary S; Weerts, Elise M; Kuwabara, Hiroto et al. (2011) Naloxone-induced cortisol predicts mu opioid receptor binding potential in specific brain regions of healthy subjects. Psychoneuroendocrinology 36:1453-9
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
Weerts, Elise M; Kim, Yu Kyeong; Wand, Gary S et al. (2008) Differences in delta- and mu-opioid receptor blockade measured by positron emission tomography in naltrexone-treated recently abstinent alcohol-dependent subjects. Neuropsychopharmacology 33:653-65
Bencherif, Badreddine; Stumpf, Martin J; Links, Jonathan M et al. (2004) Application of MRI-based partial-volume correction to the analysis of PET images of mu-opioid receptors using statistical parametric mapping. J Nucl Med 45:402-8
Bencherif, Badreddine; Wand, Gary S; McCaul, Mary E et al. (2004) Mu-opioid receptor binding measured by [11C]carfentanil positron emission tomography is related to craving and mood in alcohol dependence. Biol Psychiatry 55:255-62
Frost, J James (2003) Molecular imaging of the brain: a historical perspective. Neuroimaging Clin N Am 13:653-8

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