Modulation of the mesolimbic dopamine system by leptin
Open accessAbstract
Nutritional status modulates many forms of reward-seeking behavior, with caloric restriction increasing the drive for drugs of abuse as well as for food. Understanding the interactions between the mesolimbic dopamine (DA) system (which mediates the incentive salience of natural and artificial rewards) and the neural and hormonal systems that sense and regulate energy balance is thus of significant importance. Leptin, which is produced by adipocytes in proportion to fat content as a hormonal signal of long-term energy stores, acts via its receptor (LepRb) on multiple populations of central nervous system neurons to modulate neural circuits in response to body energy stores. Leptin suppresses feeding and plays a central role in the control of energy balance. In addition to demonstrating that leptin modulates hypothalamic and brainstem circuits to promote satiety, recent work has begun to explore the mechanisms by which leptin influences the mesolimbic DA system and related behaviors. Indeed, leptin diminishes several measures of drug and food reward, and promotes a complex set of changes in the mesolimbic DA system. While many of the details remain to be worked out, several lines of evidence suggest that leptin regulates the mesolimbic DA system via multiple neural pathways and processes, and that distinct sets of LepRb neurons each modulate unique aspects of the mesolimbic DA system and behavior in response to leptin.
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Orexigenic peptides and hormones increase VTA DA cell activity and NAc DA release when exposed to food stimuli, whereas anorexigenic ones inhibit DA firing and decrease DA release.
“Orexigenic peptides/hormones increase the activity of VTA DA cells and increase DA release in NAc (main target of VTA DA neurons) when exposed to food stimuli, whereas anorexigenic ones inhibit DA firing and decrease DA release (23).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [23]
Orexigenic signals increase VTA DA cell activity in response to food stimuli, while anorexigenic signals inhibit DA firing and decrease DA release.
“Overall, homeostatic orexigenic signals increase the activity of ventral tegmental area (VTA) DA cells when exposed to food stimuli, whereas anorexigenic ones inhibit DA firing and decrease DA release (10).”
From The Addictive Dimensionality of Obesity (2013) · cites this paper as [10]
In normal rats, leptin promotes tyrosine hydroxylase activity and amphetamine-mediated dopamine efflux in the nucleus accumbens.
“Also, in normal rats, leptin promotes tyrosine hydroxylase activity and amphetamine-mediated dopamine efflux in the nucleus accumbens”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [119]
Hypothalamic drives to maintain homeostasis can overwhelm threat avoidance and anxiety-like behaviors.
“Hypothalamic drives to maintain homeostasis (that is, to seek and consume food or water126,127) can also overwhelm threat avoidance and anxiety-like behaviors.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [126]
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- Authors
- Opland, D. M., Leinninger, G. M., & Myers
- Affiliations
- University of Michigan (US)
- Corresponding author
- Myers,, Martin G.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 1350
- Pages
- 65-70
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC2921997
- OpenAlex
- W2044324464
- Cited by
- 111
- References
- 63
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 11 · 2016: 9 · 2015: 12 · 2014: 15 · 2013: 9 · 2012: 10
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (DK078056)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- leptin, mesolimbic dopamine system, energy balance, food reward, drug reward, incentive salience, satiety, caloric restriction, food intake regulation, reward-seeking behavior
- MeSH terms
- Animals, Corpus Striatum, Dopamine, Energy Metabolism, Hypothalamus, Neurons, Reward, Ventral Tegmental Area, Leptin, Receptors, Leptin
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