Cited by 118Neurotransmitter Receptor Influence on BehaviorRegulation of Appetite and ObesityNeuroscience and Neuropharmacology Research

Selective deletion of the leptin receptor in dopamine neurons produces anxiogenic-like behavior and increases dopaminergic activity in amygdala

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Liu, J, Perez, S M, Zhang, W, Lodge, D J, Lu, X-Y·2011·Molecular Psychiatry

Abstract

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].”
  • 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.”

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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
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
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

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