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Feeding behavioral pharmacogenetics of a murine model of the OPRM1 A118G polymorphism

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Title
Feeding behavioral pharmacogenetics of a murine model of the OPRM1 A118G polymorphism
Name (type = personal)
NamePart (type = family)
Sachdeo
NamePart (type = given)
Bryn Leonard
NamePart (type = date)
1985-
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Bryn Leonard Sachdeo
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RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Bello
NamePart (type = given)
Nicholas T.
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Nicholas T. Bello
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Advisory Committee
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chair
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NamePart (type = family)
Storch
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Judith
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Judith Storch
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Advisory Committee
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RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Miller
NamePart (type = given)
Joshua
DisplayForm
Joshua Miller
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Pang
NamePart (type = given)
Zhiping
DisplayForm
Zhiping Pang
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = personal)
NamePart (type = family)
Yu
NamePart (type = given)
Lei
DisplayForm
Lei Yu
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
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theses
OriginInfo
DateCreated (encoding = w3cdtf); (keyDate = yes); (qualifier = exact)
2019
DateOther (encoding = w3cdtf); (qualifier = exact); (type = degree)
2019-10
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2019
Language
LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
Abstract (type = abstract)
Binge eating disorder (BED) is the most prevalent eating disorder, and is characterized by a perceived “loss of control” over ones food intake, resulting in the consumption of large amounts of food in short periods of time. There is currently one FDA-approved drug for the treatment of BED, lisdexamfetamine dimesylate. A common single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (OPRM1 A118G) results in an amino acid substitution (N40D) in the extracellular domain that is posited to alter receptor stability and ligand binding. The OPRM1 A118G SNP has been associated with alterations in nociception and analgesia, as well as altered susceptibility to substance abuse. GG allele status has also been associated with BED in an obese population, as well as increased preference and intake of highly-palatable foods. In this dissertation, an established rodent model of binge-like feeding was utilized to investigate the role of the homologous SNP in mice (OPRM1 A112G; N38D) in binge propensity, pharmacological efficacy, and taste and meal phenotyping in male and female mice. The 6-wk, intermittent 24-hr caloric restriction and/or 30-min subsequent binge access feeding schedules (Restrict, R; Binge, B; Restrict-Binge, RB; Naïve, N) revealed no differences in binge intakes between AA and GG genotypes in male or female mice. Following the 6-wk protocol, female mice underwent acute or chronic dosing schedules: within-group, 1x/wk dosing of vehicle (Veh; water), lisdexamfetamine dimesylate (LDX; 0.15, 0.5, 1.5 mg/kg), and sibutramine hydrochloride (Sib; 0.3, 1.0, 3.0 mg/kg); or between-group, 2-wk daily dosing of either Veh, Sib (3.0 mg/kg), or LDX (1.5 mg/kg), respectively. There was no effect of AA or GG genotype on pharmacotherapeutic efficacy in reducing binge-like feeding. Two-bottle lipid preference tests in male mice previously exposed to the 6-wk feeding schedules revealed increased preference for Intralipid (IL) in R and RB groups compared to N, for 5% IL only, and N GG had lower preference than N AA mice. Genotype differences in brief-access taste responsivity in male and female mice were observed only in sweet, nutritive carbohydrate taste stimuli. There was no effect of genotype on meal microstructure in male mice, but female GG mice had larger average meal sizes and greater total caloric meal intakes. Although there may be some elements of taste and meal patterns mediated by OPRM1 A112G SNP status, our data does not support a role for this common SNP in the predisposition to binge-like feeding nor the efficacy of pharmacotherapy. While the concept of “personalized medicine” remains intriguing, the current studies do not suggest a role for the involvement of the OPRM1 A118G SNP in binge eating disorder.
Subject (authority = RUETD)
Topic
Nutritional Sciences
Subject (authority = local)
Topic
OPRM1 A118G
Subject (authority = LCSH)
Topic
Compulsive eating -- Treatment
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_10201
PhysicalDescription
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InternetMediaType
application/pdf
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text/xml
Extent
1 online resource (xv, 138 pages) : illustrations
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/t3-sw0a-bg27
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Sachdeo
GivenName
Bryn
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2019-08-30 12:47:09
AssociatedEntity
Name
Bryn Sachdeo
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
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Copyright protected
Availability
Status
Open
Reason
Permission or license
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2019-09-21T15:28:15
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2019-09-21T15:28:15
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