Selective deletion of the leptin receptor in dopamine neurons produces anxiogenic-like behavior and increases dopaminergic activity in amygdala
Open accessAbstract
The leptin receptor (Lepr) is expressed on midbrain dopamine neurons. However, the specific role of Lepr signaling in dopamine neurons remains to be clarified. In the present study, we generated a line of conditional knockout mice lacking functional Lepr selectively on dopamine neurons (Lepr(DAT-Cre)). These mice exhibit normal body weight and feeding. Behaviorally, Lepr(DAT-Cre) mice display an anxiogenic-like phenotype in the elevated plus-maze, light-dark box, social interaction and novelty-suppressed feeding tests. Depression-related behaviors, as assessed by chronic stress-induced anhedonia, forced swim and tail-suspension tests, were not affected by deletion of Lepr in dopamine neurons. In vivo electrophysiological recordings of dopamine neurons in the ventral tegmental area revealed an increase in burst firing in Lepr(DAT-Cre) mice. Moreover, blockade of D1-dependent dopamine transmission in the central amygdala by local microinjection of the D1 antagonist SCH23390 attenuated the anxiogenic phenotype of Lepr(DAT-Cre) mice. These findings suggest that Lepr signaling in midbrain dopamine neurons has a crucial role for the expression of anxiety and for the dopamine modulation of amygdala function.
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Chronic unpredictable/mild/variable stress and chronic social defeat stress are the two most commonly used animal models of depression.
“Chronic unpredictable/mild/variable stress and chronic social defeat stress are the two most commonly used animal models of depression [31, 34–38].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [35]
The chronic unpredictable stress paradigm effectively induces anhedonia along with other depression-related behaviors, including reduced sensitivity to sucrose reward, decreased sex-related reward-seeking behavior, and despair behavior.
“we used a chronic unpredictable stress paradigm, which effectively induces anhedonia along with other depression-related behaviors [34–36], including reduced sensitivity to sucrose reward, decreased sex-related reward-seeking behavior, and despair behavior.”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [35]
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- Authors
- Liu, J., Perez, S. M., Zhang, W., Lodge, D. J., & Lu, X.-Y.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Lu, X-Y
- Venue
- Molecular Psychiatry
- Published
- 2011-04-12
- Volume
- 16
- Issue
- 10
- Pages
- 1024-1038
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC3432580
- OpenAlex
- W2060925442
- Cited by
- 118
- References
- 107
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 12 · 2022: 7 · 2021: 11 · 2020: 7 · 2019: 8 · 2018: 5 · 2017: 7 · 2016: 8 · 2015: 10 · 2014: 8 · 2013: 8 · 2012: 11
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health
- National Institute of Mental Health (MH073844, MH076929, R01MH076929, R01MH073844)
- National Institute of Neurological Disorders and Stroke (NS056237, R03NS056237)
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- leptin receptor, dopaminergic neurons, anxiety, anxiogenic behavior, central amygdala, ventral tegmental area, dopamine D1 receptor, conditional knockout mice, depression, burst firing, leptin signaling
- MeSH terms
- Action Potentials, Amygdala, Animals, Anxiety, Dopamine, Exploratory Behavior, Interpersonal Relations, Signal Transduction, Ventral Tegmental Area, Mice, Knockout, Maze Learning, Mice, Receptors, Leptin, Dopaminergic Neurons
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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