Ventral Tegmental Area Leptin Receptor Neurons Specifically Project to and Regulate Cocaine- and Amphetamine-Regulated Transcript Neurons of the Extended Central Amygdala
Open accessAbstract
Leptin acts via its receptor (LepRb) to regulate neural circuits in concert with body energy stores. In addition to acting on a number of hypothalamic structures, leptin modulates the mesolimbic dopamine (DA) system. To determine the sites at which LepRb neurons might directly influence the mesolimbic DA system, we examined the distribution of LepRb neurons and their projections within mesolimbic brain regions. Although the ventral tegmental area (VTA) contains DA LepRb neurons, LepRb neurons are absent from the amygdala and striatum. Also, LepRb-EGFPf mice (which label projections from LepRb neurons throughout the brain) reveal that few LepRb neurons project to the nucleus accumbens (NAc). In contrast, the central amygdala (CeA) and its rostral extension receive copious projections from LepRb neurons. Indeed, LepRb-specific anterograde tracing demonstrates (and retrograde tracing confirms) that VTA LepRb neurons project to the extended CeA (extCeA) but not the NAc. Consistently, leptin promotes cAMP response element-binding protein phosphorylation in the extCeA, but not NAc, of leptin-deficient animals. Furthermore, transgenic mice expressing the trans-synaptic tracer wheat germ agglutinin in LepRb neurons reveal the innervation of CeA cocaine- and amphetamine-regulated transcript (CART) neurons by LepRb neurons, and leptin suppresses the increased CeA CART expression of leptin-deficient animals. Thus, LepRb VTA neurons represent a subclass of VTA DA neurons that specifically innervates and controls the extCeA; we hypothesize that these neurons primarily modulate CeA-directed behaviors.
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VTA and/or NAc neurons express receptors for GLP-1, ghrelin, leptin, insulin, orexin, and melanocortin.
“neurons in the VTA and/or NAc express GLP-1 (24,25), ghrelin (26,27), leptin (28,29), insulin (30), orexin (31) and melanocortin receptors (32).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [29]
VTA and/or NAc neurons express receptors for GLP-1, ghrelin, leptin, insulin, orexin, and melanocortin.
“Moreover, neurons in VTA and/or nucleus accumbens (NAc) express glucagon-like peptide-1 (11,12), ghrelin (13,14), leptin (15,16), insulin (17), orexin (18), and melanocortin receptors (19).”
From The Addictive Dimensionality of Obesity (2013) · cites this paper as [16]
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- Authors
- Leshan, R. L., Opland, D. M., Louis, G. W., Leinninger, G. M., Patterson, C. M., Rhodes, C. J., Münzberg, H., & Myers, M. G.
- Affiliations
- University of Michigan (US)
- University of Chicago (US)
- Pennington Biomedical Research Center (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-04-21
- Volume
- 30
- Issue
- 16
- Pages
- 5713-5723
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2864009
- OpenAlex
- W2068778246
- Cited by
- 127
- References
- 48
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 7 · 2022: 7 · 2021: 6 · 2020: 1 · 2019: 4 · 2018: 7 · 2017: 9 · 2016: 11 · 2015: 12 · 2014: 10 · 2013: 13 · 2012: 13
- FWCI
- 6.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- American Heart Association
- Amylin Pharmaceuticals
- University of Michigan
- National Institutes of Health (DK078056, CA46592, DK20572)
- National Cancer Institute (CA46592, P30CA046592)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK078056, DK20572, P60DK020572, DK057768, R01DK057768, R01DK055267, R01DK078056, P30DK020572, P30DK036836)
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- leptin, leptin receptor, ventral tegmental area, mesolimbic dopamine system, nucleus accumbens, CREB, leptin deficiency, neuronal projections, transsynaptic tracing, wheat germ agglutinin
- MeSH terms
- Amphetamine, Amygdala, Animals, Cocaine, Mice, Obese, Mice, Transgenic, Neural Pathways, Neurons, Transcription, Genetic, Ventral Tegmental Area, Mice, Receptors, Leptin
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