title: A comparison of D2 receptor specific binding in obese and normal-weight individuals using PET with (N-[(11)C]methyl)benperidol.
abstract: Previous PET imaging studies have demonstrated mixed findings regarding dopamine D2/D3 receptor availability in obese relative to nonobese humans. Nonspecific D2/D3 radioligands do not allow for separate estimation of D2 receptor (D2R) and D3 receptor (D3R) subtypes of the D2 receptor family, which may play different roles in behavior and are distributed differently throughout the brain. These radioligands are also displaceable by endogenous dopamine, confounding interpretation of differences in receptor availability with differing levels of dopamine release. The present study used PET imaging with the D2R-selective radioligand (N-[(11)C] methyl)benperidol ([(11)C]NMB), which is nondisplaceable by endogenous dopamine, to estimate D2R specific binding (BPND) and its relationship to body mass index (BMI) and age in 15 normal-weight (mean BMI = 22.6 kg/m(2)) and 15 obese (mean BMI = 40.3 kg/m(2)) men and women. Subjects with illnesses or taking medications that interfere with dopamine signaling were excluded. Striatal D2R BPND was calculated using the Logan graphical method with cerebellum as a reference region. D2R BPND estimates were higher in putamen and caudate relative to nucleus accumbens, but did not differ between normal-weight and obese groups. BMI values did not correlate with D2R BPND . Age was negatively correlated with putamen D2R BPND in both groups. These results suggest that altered D2R specific binding is not involved in the pathogenesis of obesity per se and underscore the need for additional studies evaluating the relationship between D3R, dopamine reuptake, or endogenous dopamine release and human obesity.
authors: Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, 63110.
authors: Sarah A
authors: SA
authors: Eisenstein
authors: Jo Ann V
authors: JA
authors: Antenor-Dorsey
authors: Danuta M
authors: DM
authors: Gredysa
authors: Jonathan M
authors: JM
authors: Koller
authors: Emily C
authors: EC
authors: Bihun
authors: Samantha A
authors: SA
authors: Ranck
authors: Ana Maria
authors: AM
authors: Arbeláez
authors: Samuel
authors: S
authors: Klein
authors: Joel S
authors: JS
authors: Perlmutter
authors: Stephen M
authors: SM
authors: Moerlein
authors: Kevin J
authors: KJ
authors: Black
authors: Tamara
authors: T
authors: Hershey
mesh_terms: D000328:Adult; D000367:Age Factors; D001544:Benperidol / Q000008:administration & dosage / Q000031:analogs & derivatives; D015992:Body Mass Index; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D009765:Obesity / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism*; D009928:Organ Specificity; D049268:Positron-Emission Tomography; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
chemical_list: D017448:Receptors, Dopamine D2; C066786:N-methylbenperidol; D001544:Benperidol
keywords: NMB; dopamine; obesity
references: J Psychoactive Drugs. 2012 Apr-Jun;44(2):134-43
references: 22880541
references: J Med Phys. 2007 Jul;32(3):108-17
references: 21157530
references: J Nucl Med. 2004 Feb;45(2):192-201
references: 14960635
references: J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):844-51
references: 12810765
references: Pharmacol Biochem Behav. 2008 Jun;89(4):499-507
references: 18329700
references: Psychopharmacology (Berl). 1994 Nov;116(3):285-90
references: 7892418
references: Behav Res Methods. 2007 May;39(2):175-91
references: 17695343
references: J Nerv Ment Dis. 1995 Jun;183(6):365-9
references: 7798084
references: Synapse. 2000 Dec 1;38(3):338-42
references: 11020237
references: Diabetes Care. 2011 Apr;34(4):789-94
references: 21447659
references: J Cereb Blood Flow Metab. 1997 Aug;17(8):833-45
references: 9290581
references: J Neurosci. 2012 Jan 25;32(4):1353-9
references: 22279219
references: Synapse. 2007 Sep;61(9):748-56
references: 17568412
references: Mov Disord. 2011 Jan;26(1):100-6
references: 20960437
references: Psychol Med. 2005 Feb;35(2):245-56
references: 15841682
references: Neuropsychopharmacology. 2006 May;31(5):1016-26
references: 16237395
references: Nucl Med Biol. 2008 Apr;35(3):335-41
references: 18355689
references: Pharmacol Rev. 2011 Mar;63(1):182-217
references: 21303898
references: Neuroimage. 2008 Oct 1;42(4):1537-43
references: 18598772
references: Obes Facts. 2012;5(2):180-95
references: 22647301
references: Curr Med Chem. 2006;13(18):2139-53
references: 16918344
references: Diabetes Care. 2012 May;35(5):1105-11
references: 22432117
references: Surg Clin North Am. 2011 Dec;91(6):1163-72, vii
references: 22054146
references: J Cereb Blood Flow Metab. 1996 Sep;16(5):834-40
references: 8784228
references: Neuropsychopharmacology. 1997 Feb;16(2):174-82
references: 9015800
references: Adv Neurol. 1993;60:494-500
references: 8420177
references: Neuroimage. 2008 Jun;41(2):636-47
references: 18413289
references: Ann N Y Acad Sci. 1993 Sep 24;695:81-5
references: 8239318
references: Biochem Pharmacol. 2012 Oct 1;84(7):882-90
references: 22781742
references: J Nucl Med. 1995 Jul;36(7):1182-90
references: 7790942
references: Synapse. 2012 Sep;66(9):770-80
references: 22535514
references: Lancet. 2001 Feb 3;357(9253):354-7
references: 11210998
references: J Nucl Med. 1997 Oct;38(10):1614-23
references: 9379202
references: Appetite. 2012 Aug;59(1):27-33
references: 22445776
references: Int J Neuropsychopharmacol. 2012 Mar;15(2):149-61
references: 21745436
references: Synapse. 1993 Apr;13(4):350-6
references: 8480281
references: EJNMMI Res. 2011 Dec 16;1(1):37
references: 22214469
references: Am J Psychiatry. 2001 Dec;158(12):2015-21
references: 11729018
references: J Neurochem. 1985 Mar;44(3):835-44
references: 2579198
references: Int J Rad Appl Instrum A. 1992 Jul;43(7):913-7
references: 1321101
references: Synapse. 1993 Jun;14(2):169-77
references: 8101394
references: Nucl Med Biol. 1995 Aug;22(6):809-15
references: 8535343
references: Diabetes Care. 2010 Jan;33 Suppl 1:S11-61
references: 20042772
references: J Neurosci. 2010 Sep 29;30(39):13105-9
references: 20881128
references: Nucl Med Biol. 1999 Jul;26(5):519-27
references: 10473190
references: J Nucl Med. 1990 Dec;31(12):2015-21
references: 2148346