Leptin/LepRb in the ventral tegmental area mediates anxiety-related behaviors

Jing Liu, Ming Guo, Xinyun Lu

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Leptin, an adipose-derived hormone, has been implicated in emotional regulation. We have previously shown that systemic administration of leptin produces anxiolytic-like effects and deletion of the leptin receptor, LepRb, in midbrain dopamine neurons leads to an anxiogenic phenotype. This study investigated whether activation or deletion of LepRb in the ventral tegmental area of adult mice is capable of inducing anxiolytic and anxiogenic effects, respectively. Methods: Mice were cannulated in the ventral tegmental area and received bilateral intra-ventral tegmental area infusions of leptin or the JAK2/STAT3 inhibitor AG490. Anxiety-like behaviors were assessed using the elevated plus-maze, light-dark box, and novelty suppressed feeding tests. Deletion of LepRb in the ventral tegmental area was achieved by bilateral injection of AAV-Cre into the ventral tegmental area of adult Leprfox/fox mice. Anxiety-related behaviors were evaluated 3 weeks after viral injection. Results: Intra-ventral tegmental area infusions of leptin reduced anxiety-like behaviors, as indicated by increased percent open-arm time and open-arm entries in the elevated plus-maze test, increased time spent in the light side and decreased latency to enter the light side of the light-dark box, and decreased latency to feed in the novelty suppressed feeding test. Blockade of JAK2/STAT3 signaling in the ventral tegmental area by AG490 attenuated the anxiolytic effect produced by systemic administration of leptin. Leprfox/fox mice injected with AAV-Cre into the ventral tegmental area showed decreased leptin-induced STAT3 phosphorylation and enhanced anxiety-like behaviors in the elevated plus-maze test and the novelty suppressed feeding test. Conclusions: These fndings suggest that leptin-LepRb signaling in the ventral tegmental area plays an important role in the regulation of anxiety-related behaviors.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalInternational Journal of Neuropsychopharmacology
Volume19
Issue number2
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

Ventral Tegmental Area
Leptin
Anxiety
Anti-Anxiety Agents
Light
Leptin Receptors
Injections
Dopaminergic Neurons
Mesencephalon
Phosphorylation
Hormones
Phenotype

Keywords

  • Elevated plus-maze test
  • JAK2/STAT3
  • Leptin receptor
  • Light-dark box
  • Novelty suppessed feeding

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Leptin/LepRb in the ventral tegmental area mediates anxiety-related behaviors. / Liu, Jing; Guo, Ming; Lu, Xinyun.

In: International Journal of Neuropsychopharmacology, Vol. 19, No. 2, 01.01.2016, p. 1-11.

Research output: Contribution to journalArticle

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abstract = "Background: Leptin, an adipose-derived hormone, has been implicated in emotional regulation. We have previously shown that systemic administration of leptin produces anxiolytic-like effects and deletion of the leptin receptor, LepRb, in midbrain dopamine neurons leads to an anxiogenic phenotype. This study investigated whether activation or deletion of LepRb in the ventral tegmental area of adult mice is capable of inducing anxiolytic and anxiogenic effects, respectively. Methods: Mice were cannulated in the ventral tegmental area and received bilateral intra-ventral tegmental area infusions of leptin or the JAK2/STAT3 inhibitor AG490. Anxiety-like behaviors were assessed using the elevated plus-maze, light-dark box, and novelty suppressed feeding tests. Deletion of LepRb in the ventral tegmental area was achieved by bilateral injection of AAV-Cre into the ventral tegmental area of adult Leprfox/fox mice. Anxiety-related behaviors were evaluated 3 weeks after viral injection. Results: Intra-ventral tegmental area infusions of leptin reduced anxiety-like behaviors, as indicated by increased percent open-arm time and open-arm entries in the elevated plus-maze test, increased time spent in the light side and decreased latency to enter the light side of the light-dark box, and decreased latency to feed in the novelty suppressed feeding test. Blockade of JAK2/STAT3 signaling in the ventral tegmental area by AG490 attenuated the anxiolytic effect produced by systemic administration of leptin. Leprfox/fox mice injected with AAV-Cre into the ventral tegmental area showed decreased leptin-induced STAT3 phosphorylation and enhanced anxiety-like behaviors in the elevated plus-maze test and the novelty suppressed feeding test. Conclusions: These fndings suggest that leptin-LepRb signaling in the ventral tegmental area plays an important role in the regulation of anxiety-related behaviors.",
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