title: Imaging of brain dopamine pathways: implications for understanding obesity.
abstract: Obesity is typically associated with abnormal eating behaviors. Brain imaging studies in humans implicate the involvement of dopamine (DA)-modulated circuits in pathologic eating behavior(s). Food cues increase striatal extracellular DA, providing evidence for the involvement of DA in the nonhedonic motivational properties of food. Food cues also increase metabolism in the orbitofrontal cortex indicating the association of this region with the motivation for food consumption. Similar to drug-addicted subjects, striatal DA D2 receptor availability is reduced in obese subjects, which may predispose obese subjects to seek food as a means to temporarily compensate for understimulated reward circuits. Decreased DA D2 receptors in the obese subjects are also associated with decreased metabolism in prefrontal regions involved in inhibitory control, which may underlie their inability to control food intake. Gastric stimulation in obese subjects activates cortical and limbic regions involved with self-control, motivation, and memory. These brain regions are also activated during drug craving in drug-addicted subjects. Obese subjects have increased metabolism in the somatosensory cortex, which suggests an enhanced sensitivity to the sensory properties of food. The reduction in DA D2 receptors in obese subjects coupled with the enhanced sensitivity to food palatability could make food their most salient reinforcer putting them at risk for compulsive eating and obesity. The results from these studies suggest that multiple but similar brain circuits are disrupted in obesity and drug addiction and suggest that strategies aimed at improving DA function might be beneficial in the treatment and prevention of obesity.
authors: Medical Department (GJW, JSF), Brookhaven National Laboratory, Upton, NY; Mount Sinai School of Medicine (GJW, JSF), New York, NY; and National Institute of Drug Abuse/National Institute of Alcohol Abuse and Alcoholism (NDV, PKT), Bethesda, MD.
authors: Gene-Jack
authors: GJ
authors: Wang
authors: Nora D
authors: ND
authors: Volkow
authors: Panayotis K
authors: PK
authors: Thanos
authors: Joanna S
authors: JS
authors: Fowler
references: Science. 2007 Dec 7;318(5856):1642-5
references: 18063800
references: Am J Psychiatry. 2001 Dec;158(12):2015-21
references: 11729018
references: Womens Health Issues. 2008 Jul-Aug;18(4):281-91
references: 18468920
references: Neuroscience. 2004;124(1):71-9
references: 14960340
references: Int J Obes (Lond). 2008 Jul;32(7):1171-9
references: 18475275
references: Diabetes Obes Metab. 2007 May;9(3):360-8
references: 17391164
references: Annu Rev Med. 2008;59:147-62
references: 17845135
references: Philos Trans R Soc Lond B Biol Sci. 2008 Oct 12;363(1507):3191-200
references: 18640912
references: Neurosci Lett. 2008 Feb 6;431(3):231-5
references: 18178315
references: Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11696-701
references: 12975524
references: Neuroreport. 2002 Jul 2;13(9):1141-5
references: 12151757
references: Behav Brain Res. 2006 Dec 15;175(2):415-9
references: 17000016
references: Neuroscience. 2005;134(3):737-44
references: 15987666
references: Nature. 2007 Nov 1;450(7166):106-9
references: 17934448
references: Am J Clin Nutr. 2006 Jun;83(6):1297-305
references: 16762940
references: J Neurosci. 1999 Aug 1;19(15):6610-4
references: 10414988
references: Cell Metab. 2008 May;7(5):400-9
references: 18460331
references: Science. 1996 Mar 15;271(5255):1586-9
references: 8599115
references: N Engl J Med. 2008 Jul 17;359(3):229-41
references: 18635428
references: Neuropsychopharmacology. 2003 Jul;28(7):1272-80
references: 12700694
references: Front Horm Res. 2008;36:165-181
references: 18230902
references: Neurosci Lett. 1987 Aug 18;79(1-2):138-44
references: 2959886
references: FASEB J. 2008 Aug;22(8):2740-6
references: 18477764
references: Neuroreport. 2002 Jul 2;13(9):1151-5
references: 12151759
references: Eur J Neurosci. 2007 May;25(9):2885-904
references: 17561849
references: J Gerontol A Biol Sci Med Sci. 2008 May;63(5):529-35
references: 18511759
references: J Neurosci. 2003 Apr 1;23(7):2882-8
references: 12684475
references: Science. 1983 Apr 22;220(4595):431-3
references: 6836286
references: J Neurosci. 2007 Nov 14;27(46):12700-6
references: 18003850
references: Nat Neurosci. 2005 May;8(5):555-60
references: 15856062
references: Neuroimage. 2008 Feb 15;39(4):1559-69
references: 18096409
references: Annu Rev Physiol. 2008;70:537-56
references: 17937601
references: Am J Physiol Regul Integr Comp Physiol. 2006 Nov;291(5):R1236-9
references: 16763080
references: Neurochem Res. 2007 Oct;32(10):1772-82
references: 17721820
references: Neuropharmacology. 2006 Jun;50(8):953-63
references: 16549074
references: Proc Nutr Soc. 2007 Feb;66(1):96-112
references: 17343776
references: Obesity (Silver Spring). 2007 Aug;15(8):2027-42
references: 17712121
references: J Gerontol A Biol Sci Med Sci. 2006 Nov;61(11):1166-70
references: 17167157
references: Physiol Behav. 2002 Jul;76(3):353-64
references: 12117572
references: Science. 2007 Jan 26;315(5811):531-4
references: 17255515
references: Physiol Behav. 2006 Nov 30;89(4):611-6
references: 17045623
references: Neuroimage. 2008 Feb 15;39(4):1824-31
references: 18155924
references: Synapse. 2008 Jan;62(1):50-61
references: 17960763
references: Neuroimage. 2008 Mar 1;40(1):275-9
references: 18096411
references: Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15641-5
references: 17023542
references: Brain Res Brain Res Rev. 1998 Dec;28(3):309-69
references: 9858756
references: JAMA. 2007 Oct 10;298(14):1661-73
references: 17925518
references: Am J Clin Nutr. 1999 Jun;69(6):1189-93
references: 10357738
references: Neuroimage. 2008 Oct 1;42(4):1537-43
references: 18598772
references: Neuroendocrinology. 2005;81(1):49-55
references: 15809512
references: J Neurosci. 2001 Sep 1;21(17):6897-904
references: 11517277
references: Curr Opin Neurobiol. 2003 Aug;13(4):500-5
references: 12965300
references: Nat Clin Pract Endocrinol Metab. 2006 Aug;2(8):447-58
references: 16932334
references: Neuroimage. 2003 Aug;19(4):1381-94
references: 12948696
references: Neurosci Biobehav Rev. 2004 Nov;28(7):771-84
references: 15555683
references: Neuroimage. 2003 Aug;19(4):1709-15
references: 12948725
references: JAMA. 2006 Apr 5;295(13):1549-55
references: 16595758
references: Am J Clin Nutr. 1997 Aug;66(2):239-46
references: 9250100
references: J Neurosci. 2003 Sep 3;23(22):8092-7
references: 12954871
references: Behav Brain Res. 2001 Dec 14;127(1-2):13-23
references: 11718882
references: Physiol Behav. 1990 Mar;47(3):477-81
references: 2359756
references: J Med Chem. 2008 Mar 27;51(6):1800-10
references: 18307287
references: Neuroimage. 2004 Apr;21(4):1790-7
references: 15050599
references: Synapse. 2006 Dec 1;60(7):485-95
references: 16952157
references: Neuroscience. 2006 Nov 17;143(1):309-17
references: 17049180
references: Biochem Pharmacol. 2008 Jan 1;75(1):63-75
references: 17719013
references: BJOG. 2006 Oct;113(10):1126-33
references: 16827826
references: Lancet. 2001 Feb 3;357(9253):354-7
references: 11210998
references: Brain Res Mol Brain Res. 2005 Apr 27;135(1-2):150-61
references: 15857678
references: Alzheimers Dement. 2007 Apr;3(2):98-108
references: 18379636
references: ChemMedChem. 2008 May;3(5):788-93
references: 18306190
references: J Clin Endocrinol Metab. 2008 Jun;93(6):2027-34
references: 18539769
references: Ann N Y Acad Sci. 2003 Apr;985:251-62
references: 12724163
references: Appetite. 2004 Aug;43(1):11-3
references: 15262012
references: Physiol Behav. 2007 Jul 24;91(4):449-58
references: 17543357
references: J Clin Invest. 2006 Dec;116(12):3229-39
references: 17060947
references: Physiol Behav. 1997 Jul;62(1):15-21
references: 9226337
references: Physiol Behav. 2007 Aug 15;91(5):459-72
references: 17081571
references: Science. 2000 Sep 22;289(5487):2122-5
references: 11000114
references: Trends Neurosci. 2007 May;30(5):220-7
references: 17400299
references: Pharmacol Biochem Behav. 2008 Jun;89(4):499-507
references: 18329700
references: Neuroimage. 2004 Dec;23(4):1486-93
references: 15589112
references: J Clin Psychiatry. 2007 Aug;68(8):1226-9
references: 17854247
references: Cereb Cortex. 2008 Jul;18(7):1549-59
references: 18056086
references: Psychopharmacology (Berl). 2001 Jun;156(1):32-41
references: 11465631
references: Neurogastroenterol Motil. 2008 May;20 Suppl 1:64-72
references: 18402643
references: J Appl Physiol (1985). 2006 Oct;101(4):1237-42
references: 16778001
references: Eur J Pharmacol. 2003 Nov 7;480(1-3):125-31
references: 14623356
references: Brain Res Bull. 1994;35(1):41-9
references: 7953756
references: Neurosci Biobehav Rev. 2008;32(1):20-39
references: 17617461
references: N Engl J Med. 2003 Sep 4;349(10):941-8
references: 12954742
references: CNS Spectr. 2006 Nov;11(11):855-62
references: 17075557
references: Int J Obes (Lond). 2007 Dec;31(12):1849-58
references: 17593902
references: Behav Neurosci. 1998 Jun;112(3):630-5
references: 9676978
references: Recent Pat CNS Drug Discov. 2006 Nov;1(3):305-14
references: 18221212
references: Neuroreport. 2003 Aug 26;14(12):1609-12
references: 14502085
references: Neuroreport. 2000 Jul 14;11(10):2069-72
references: 10923645
references: Behav Brain Res. 2002 Aug 21;134(1-2):123-30
references: 12191798
references: J Neurochem. 2002 Jan;80(2):219-29
references: 11902112
references: JAMA. 2007 Mar 7;297(9):969-77
references: 17341711
references: Psychopharmacology (Berl). 2004 Apr;173(1-2):217-20
references: 14726998
references: Cereb Cortex. 2008 Mar;18(3):648-51
references: 17591596
references: JAMA. 2005 Jan 5;293(1):43-53
references: 15632335
references: Int J Obes Relat Metab Disord. 2004 Mar;28(3):370-7
references: 14676847
references: Trends Neurosci. 2007 Aug;30(8):375-81
references: 17604133
references: Eur J Neurosci. 2007 Aug;26(4):1067-76
references: 17714197
references: Physiol Behav. 2006 Sep 30;89(2):226-34
references: 16854442
references: Diabetes. 2005 Jul;54(7):1899-906
references: 15983188
references: Psychoneuroendocrinology. 2005 Jun;30(5):496-504
references: 15721060
references: Brain Res. 1992 Sep 4;589(2):338-40
references: 1356596
references: Cochrane Database Syst Rev. 2008 Apr 16;(2):CD005381
references: 18425918
references: Science. 2007 Sep 7;317(5843):1355
references: 17690262
references: Am J Psychiatry. 2002 Oct;159(10):1642-52
references: 12359667
references: Behav Brain Res. 1993 Jun 30;55(2):131-41
references: 7689319
references: Electroencephalogr Clin Neurophysiol. 1995 May;96(3):236-47
references: 7750449
references: Psychopharmacology (Berl). 2007 Apr;191(3):567-78
references: 17093978
references: Neuropsychopharmacology. 2008 Feb;33(3):513-23
references: 17487228
references: Appetite. 2003 Aug;41(1):7-13
references: 12880616
references: Clin Exp Pharmacol Physiol. 2006 Sep;33(9):857-62
references: 16922821
references: Int J Obes Relat Metab Disord. 2002 Apr;26(4):437-41
references: 12075568
references: Eur J Pharmacol. 2000 Sep 29;405(1-3):303-27
references: 11033337
references: Neuroscience. 2005;132(1):219-32
references: 15780480
references: J Clin Invest. 2007 Jan;117(1):13-23
references: 17200702
references: Synapse. 1993 Jun;14(2):169-77
references: 8101394
references: Physiol Behav. 2005 Mar 16;84(3):363-9
references: 15763573
references: Clin Pharmacol Ther. 2007 May;81(5):748-52
references: 17438540
references: Nutr Rev. 2007 Dec;65(12 Pt 1):517-34
references: 18236691
references: Curr Opin Pharmacol. 2007 Feb;7(1):69-76
references: 17174602
references: Am J Physiol Regul Integr Comp Physiol. 2005 Jan;288(1):R25-33
references: 15590994
references: Exp Brain Res. 2005 Oct;166(3-4):345-57
references: 16028032
references: Am J Physiol Regul Integr Comp Physiol. 2004 Jan;286(1):R31-7
references: 12933362
references: Physiol Rev. 1998 Jan;78(1):189-225
references: 9457173
references: Int J Neuropsychopharmacol. 2007 Apr;10(2):167-81
references: 16426478
references: Ann N Y Acad Sci. 2008;1129:35-46
references: 18591467
references: Arch Gen Psychiatry. 2006 Sep;63(9):999-1008
references: 16953002
references: Curr Opin Neurobiol. 2004 Apr;14(2):139-47
references: 15082317
references: Neuron. 2001 Jun;30(3):819-28
references: 11430814
references: Philos Trans R Soc Lond B Biol Sci. 2006 Jul 29;361(1471):1149-58
references: 16874930
references: Ageing Res Rev. 2006 Aug;5(3):332-53
references: 16899414
references: Physiol Behav. 2008 Jun 9;94(3):474-80
references: 18420235
references: Brain Res Brain Res Rev. 2005 Jul;49(1):77-105
references: 15960988
references: Diabetes. 2006 Nov;55(11):2986-92
references: 17065334
references: Psychopharmacology (Berl). 1990;100(3):355-60
references: 2315433
references: Synapse. 2002 Jun 1;44(3):175-80
references: 11954049
references: Neuroendocrinology. 2000 Jan;71(1):68-78
references: 10644901
references: Physiol Behav. 2005 Dec 15;86(5):773-95
references: 16289609
references: Psychopharmacology (Berl). 2007 Apr;191(3):439-59
references: 17318502
references: Neuroimage. 2005 Jan 15;24(2):436-43
references: 15627585
references: Brain Res. 2005 Nov 9;1061(2):88-96
references: 16226228
references: Nature. 1996 May 16;381(6579):245-8
references: 8622768
references: Ann N Y Acad Sci. 2001 Apr;928:316-26
references: 11795523
references: J Neurosci. 2005 Mar 9;25(10):2733-40
references: 15758183
references: J Mol Neurosci. 2003;20(3):213-21
references: 14501000
references: Mol Endocrinol. 2008 May;22(5):1023-31
references: 18202144
references: JAMA. 2003 Apr 9;289(14):1820-5
references: 12684361