Reduced nicotine reward in obesity: cross-comparison in human and mouse.
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.
Blendy
Julie A
JA
Department of Pharmacology, 125 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104-6084, USA. blendy@pharm.med.upenn.edu
Strasser
Andrew
A
Walters
Carrie L
CL
Perkins
Kenneth A
KA
Patterson
Freda
F
Berkowitz
Robert
R
Lerman
Caryn
C
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
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D017450:Receptors, Opioid, mu; D009538:Nicotine; D000242:Cyclic AMP
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