title: Reduced nicotine reward in obesity: cross-comparison in human and mouse.
abstract: BACKGROUND
  Tobacco use and obesity lead to significant morbidity and mortality.
  
  
  OBJECTIVE
  This study was conducted to investigate the factors maintaining smoking behavior in lean and obese individuals by utilizing a mouse/human cross-validation model of nicotine reward.
  
  
  METHODS
  In humans, a cigarette choice paradigm was used to examine the relative reinforcing value of nicotine in obese and non-obese smokers. Conditioned place preference (CPP) for nicotine was assessed in mice fed standard low fat rodent chow and mice rendered obese by a high fat diet.
  
  
  RESULTS
  In humans, obese smokers self-administered nicotine via cigarettes significantly less often than non-obese smokers and showed attenuated hedonic effects of nicotine-containing cigarettes compared to denicotinized cigarettes. Similarly, mice exposed to a high fat diet did not exhibit nicotine CPP, relative to control mice. mRNA levels for mu-opiate and leptin receptors were also downregulated in the ventral tegmental area of these mice.
  
  
  CONCLUSIONS
  Together, these studies provide the first evidence for reduced nicotine reward in obese subjects and suggest that this may be mediated by dietary influences on the endogenous opioid system.
authors.affiliation: Department of Pharmacology, 125 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104-6084, USA. blendy@pharm.med.upenn.edu
authors.forename: Julie A
authors.initials: JA
authors.lastname: Blendy
authors.forename: Andrew
authors.initials: A
authors.lastname: Strasser
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Walters
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Perkins
authors.forename: Freda
authors.initials: F
authors.lastname: Patterson
authors.forename: Robert
authors.initials: R
authors.lastname: Berkowitz
authors.forename: Caryn
authors.initials: C
authors.lastname: Lerman
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009538:Nicotine / Q000008:administration & dosage*; D009765:Obesity / Q000523:psychology*; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000235:genetics; D054411:Receptors, Leptin; D017450:Receptors, Opioid, mu / Q000235:genetics; D012201:Reward; D012907:Smoking / Q000523:psychology*; D017557:Ventral Tegmental Area / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D017450:Receptors, Opioid, mu; D009538:Nicotine; D000242:Cyclic AMP
references.citation: Peptides. 1987 Nov-Dec;8(6):1035-43
references.pmid: 3441443
references.citation: Ann Intern Med. 2004 Mar 16;140(6):426-33
references.pmid: 15023708
references.citation: N Engl J Med. 2003 Apr 24;348(17):1625-38
references.pmid: 12711737
references.citation: Psychopharmacology (Berl). 1999 Apr;143(4):339-46
references.pmid: 10367550
references.citation: Prog Neurobiol. 1998 Dec;56(6):613-72
references.pmid: 9871940
references.citation: J Pharmacol Exp Ther. 1992 Nov;263(2):451-6
references.pmid: 1331399
references.citation: Psychopharmacology (Berl). 2000 Dec;153(1):31-43
references.pmid: 11255927
references.citation: Psychopharmacology (Berl). 2005 Jun;180(1):41-8
references.pmid: 15682300
references.citation: Brain Res. 1995 Jul 10;685(1-2):129-34
references.pmid: 7583238
references.citation: Neurosci Lett. 1990 May 18;113(1):40-6
references.pmid: 2164174
references.citation: Psychopharmacology (Berl). 1999 Jul;145(1):1-20
references.pmid: 10445368
references.citation: Nicotine Tob Res. 1999;1 Suppl 2:S133-7; discussion S139-40
references.pmid: 11768171
references.citation: Physiol Behav. 2001 May;73(1-2):229-34
references.pmid: 11399316
references.citation: Psychopharmacology (Berl). 1995 Jan;117(1):2-10; discussion 14-20
references.pmid: 7724697
references.citation: Nicotine Tob Res. 2001 Nov;3(4):383-90
references.pmid: 11694206
references.citation: J Neurosci. 2002 Dec 15;22(24):10935-40
references.pmid: 12486188
references.citation: Nicotine Tob Res. 2001 May;3(2):101-9
references.pmid: 11403723
references.citation: Pharmacogenomics J. 2004;4(3):184-92
references.pmid: 15007373
references.citation: Psychopharmacology (Berl). 1988;96(1):29-35
references.pmid: 2852377
references.citation: Pharmacol Biochem Behav. 1996 Oct;55(2):257-63
references.pmid: 8951962
references.citation: Br J Addict. 1992 Feb;87(2):193-205
references.pmid: 1554996
references.citation: Psychopharmacology (Berl). 1993;112(2-3):339-42
references.pmid: 7871039
references.citation: Nicotine Tob Res. 2003 Oct;5(5):695-709
references.pmid: 14577986
references.citation: JAMA. 2004 Mar 10;291(10):1238-45
references.pmid: 15010446
references.citation: Exp Clin Psychopharmacol. 2000 Aug;8(3):326-32
references.pmid: 10975620
references.citation: Drug Alcohol Depend. 1988 May;21(2):99-104
references.pmid: 3262051
references.citation: Neurosci Lett. 1986 Dec 12;72(2):169-73
references.pmid: 3027625
references.citation: Brain Res. 1999 Nov 27;848(1-2):114-23
references.pmid: 10612703
references.citation: Psychopharmacology (Berl). 1986;90(1):101-5
references.pmid: 3094051
references.citation: Brain Res. 2003 Feb 21;964(1):107-15
references.pmid: 12573518
references.citation: Br J Addict. 1991 Sep;86(9):1119-27
references.pmid: 1932883
references.citation: Physiol Behav. 1988;43(3):371-4
references.pmid: 2902651
references.citation: Pharmacol Biochem Behav. 1997 Feb;56(2):235-41
references.pmid: 9050080
references.citation: Psychopharmacology (Berl). 1999 Nov;147(2):210-6
references.pmid: 10591889
references.citation: MMWR Morb Mortal Wkly Rep. 2002 Jul 26;51(29):642-5
references.pmid: 12186222
references.citation: J Consult Clin Psychol. 1993 Oct;61(5):768-77
references.pmid: 8245274
references.citation: Nature. 1997 Nov 27;390(6658):401-4
references.pmid: 9389479
references.citation: Mol Pharmacol. 2003 Dec;64(6):1410-8
references.pmid: 14645671
references.citation: Brain Res. 2002 Oct 25;953(1-2):215-22
references.pmid: 12384255
references.citation: Br J Pharmacol. 1989 Sep;98(1):135-40
references.pmid: 2804543
references.citation: Psychopharmacology (Berl). 2000 Jul;151(1):49-54
references.pmid: 10958116
references.citation: Annu Rev Neurosci. 1984;7:223-55
references.pmid: 6324644
references.citation: Exp Clin Psychopharmacol. 2001 Aug;9(3):243-50
references.pmid: 11534534
references.citation: Science. 2000 Jan 7;287(5450):125-8
references.pmid: 10615045
references.citation: Pharmacol Biochem Behav. 2000 Sep;67(1):71-81
references.pmid: 11113486
references.citation: Nat Neurosci. 2002 Aug;5(8):727-8
references.pmid: 12101402
references.citation: Psychopharmacology (Berl). 2000 May;149(4):401-8
references.pmid: 10867968
references.citation: Addiction. 1997 Feb;92(2):207-17
references.pmid: 9158232
references.citation: J Neurosci. 2002 May 1;22(9):3306-11
references.pmid: 11978804
references.citation: Nature. 1998 Oct 22;395(6704):763-70
references.pmid: 9796811
references.citation: Am J Physiol. 1996 May;270(5 Pt 2):R1019-24
references.pmid: 8928900
references.citation: J Pharmacol Exp Ther. 2003 Apr;305(1):1-8
references.pmid: 12649346
references.citation: Neurosci Biobehav Rev. 1984 Winter;8(4):503-13
references.pmid: 6151160
references.citation: Arch Intern Med. 2001 Jul 9;161(13):1581-6
references.pmid: 11434789
references.citation: Pharmacol Biochem Behav. 2004 Jan;77(1):29-37
references.pmid: 14724039
references.citation: Nicotine Tob Res. 2003 Dec;5(6):851-7
references.pmid: 14750508
references.citation: Psychol Addict Behav. 2002 Mar;16(1):22-7
references.pmid: 11934082
references.citation: JAMA. 2002 Oct 9;288(14):1723-7
references.pmid: 12365955
references.citation: Brain Res. 1994 Aug 8;653(1-2):278-84
references.pmid: 7982062
references.citation: Neurosci Biobehav Rev. 1993 Spring;17(1):21-41
references.pmid: 8455815
references.citation: J Neurochem. 1995 Apr;64(4):1878-83
references.pmid: 7891117
references.citation: Psychopharmacology (Berl). 2003 Jul;168(1-2):42-3
references.pmid: 12719965
references.citation: Peptides. 1991 Jan-Feb;12(1):161-6
references.pmid: 2052491
references.citation: Arch Med Res. 2004 Jul-Aug;35(4):329-33
references.pmid: 15325508
references.citation: Nicotine Tob Res. 2002 Nov;4(4):459-66
references.pmid: 12521405
references.citation: Health Psychol. 2002 Jul;21(4):332-9
references.pmid: 12090675
references.citation: Arch Intern Med. 2001 Feb 26;161(4):546-50
references.pmid: 11252113
references.citation: Pharmacol Biochem Behav. 1998 Mar;59(3):767-73
references.pmid: 9512084
references.citation: J Neurosci. 2003 Apr 1;23(7):2882-8
references.pmid: 12684475