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Cited by 135Neurotransmitter Receptor Influence on BehaviorRegulation of Appetite and ObesityEating Disorders and Behaviors

Food restriction markedly increases dopamine D2 receptor (D2R) in a rat model of obesity as assessed with in‐vivo μPET imaging ([11C] raclopride) and in‐vitro ([3H] spiperone) autoradiography

Thanos, Panayotis K., Michaelides, Michael, Piyis, Yiannis K., Wang, Gene‐Jack, Volkow, Nora D.·2008·Synapse
DOI 10.1002/syn.20468
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Abstract

Introduction:Dopamine (DA) regulates food intake by modulating food reward and motivation but its involvement in obesity is much less understood. Recent evidence points to the involvement of leptin in the DA‐related modulation of food intake. Here we assess DA D2 receptors (D2R) in a genetic rodent obesity model characterized by leptin‐receptor deficiency and assess the influence of food restriction on these receptors.Methods:We compared D2R levels between Zucker Obese (fa/fa) and Lean (Fa/Fa) rats at 1 and 4 months of age and in two different feeding conditions (restricted and unrestricted food access) using in‐vivo μPET imaging ([11 C] raclopride, which is a method sensitive to competition with endogenous DA) and in‐vitro ([3 H] spiperone washed to ensure no competition with endogenous DA) autoradiography (ARG).Results:Both ARG and μPET showed that D2R were higher at 1 month than at 4 months of age and that food restricted animals had higher D2R than unrestricted animals. However there were significant differences in the results obtained at 4 months between ARG and μPET. ARG showed that at 1 month and at 4 months unrestricted lean rats (Le U) had significantly higher D2R binding than obese unrestricted rats (Ob U) but showed no differences between restricted obese (Ob R) and restricted lean rats (Le R). It also showed that D2R decline between 1 and 4 months of age was significantly attenuated in food restricted rats [both obese and lean]. In contrast, μPET showed that at 4 months of age, Ob U showed greater D2R availability than Le U rats but like ARG showed no differences between Ob R and Le R rats.Conclusion:The lower D2R binding in Ob U than Le U rats observed with ARG most likely reflects decreases in striatal D2 receptors levels whereas the increased availability observed with μPET is likely to reflect reduced DA release (resulting in decreased competition with endogenous DA). Lack of a significant difference between Ob R and Le R suggests that the differences in dopamine activity and D2R levels between Ob and Le Zucker rats are modulated by access to food. The ARG finding of an attenuation of the age‐related loss of D2R binding corroborates previous studies of the salutary effects of food restriction in the aging process. Because [11 C] raclopride is sensitive to competition with endogenous DA, the higher D2R binding in obese rats with raclopride despite the lower D2R levels shown with spiperone could reflect lower extracellular DA in the Ob rats and merits further investigation. Synapse 62:50–61, 2008. Published 2007 Wiley‐Liss, Inc.

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  • Changes in neuroendocrine hormones triggered by food restriction are dynamically associated with brain DA signalling, and addictive personality is related to maladaptive eating behaviours following bariatric surgery.

    “This is consistent with preclinical (40) and clinical (41) studies showing dynamic associations between the changes in neuroendocrine hormones (e.g. insulin, leptin, ghrelin) triggered by food restriction and brain DA signalling and those of recent reports of a relationship between addictive personality and maladaptive eating behaviours following bariatric surgery (42,43).”

    From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [40]

  • Experimental research with rats has revealed that acute food deprivation and chronic caloric deprivation results in increased DA release at feeding and increased D2 receptor binding.

    “Experimental research with rats has revealed that acute food deprivation and chronic caloric deprivation results in increased DA release at feeding and increased D2 receptor binding (Thanos et al., 2008)”

    From Caloric deprivation increases responsivity of attention and reward brain regions to intake, anticipated intake, and images of palatable foods (2013) · cites this paper as Thanos et al., 2008

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Authors
Thanos, P. K., Michaelides, M., Piyis, Y. K., Wang, G., & Volkow, N. D.
Affiliations
  • National Institutes of Health (US)
  • Brookhaven National Laboratory (US)
Corresponding author
Thanos, Panayotis K.
ORCID
Venue
Synapse
Publisher
Wiley
Published
2007-10-25
Volume
62
Issue
1
Pages
50-61
ISSN
  • 0887-4476 (ISSN-L)
  • 1098-2396
DOI
10.1002/syn.20468
OpenAlex
W2112444367
Cited by
135
References
62
Citations by year
2025: 4 · 2024: 2 · 2023: 3 · 2022: 8 · 2021: 3 · 2020: 3 · 2019: 9 · 2018: 12 · 2017: 5 · 2016: 12 · 2015: 7 · 2014: 11 · 2013: 5 · 2012: 17
FWCI
3.04
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Synapse (publishedVersion, public-domain)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute on Alcohol Abuse and Alcoholism (AA-07611, R01AA011034, AA 07574, AA11034, T32AA007574)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
Keywords
dopamine D2 receptor, dietary restriction, obesity, leptin receptor deficiency, Zucker fatty rats, [11C]raclopride PET, striatum, dopamine release, food reward, aging, genetic obesity model, food intake regulation
MeSH terms
Age Factors, Animals, Apomorphine, Appetite Regulation, Autoradiography, Brain, Disease Models, Animal, Dopamine, Eating, Food Deprivation, Male, Motor Activity, Obesity, Rats, Zucker, Spiperone, Tritium, Receptors, Dopamine D2, Dopamine Agonists, Raclopride, Positron-Emission Tomography, Rats, Receptors, Leptin, In Vitro Techniques

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