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

J. Liu, S. M. Perez, W. Zhang, D. J. Lodge, Xinyun Lu

Research output: Contribution to journalArticle

61 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1024-1038
Number of pages15
JournalMolecular Psychiatry
Volume16
Issue number10
DOIs
StatePublished - Oct 1 2011
Externally publishedYes

Fingerprint

Leptin Receptors
Dopaminergic Neurons
Amygdala
Mesencephalon
Dopamine
Anhedonia
Hindlimb Suspension
Phenotype
Ideal Body Weight
Ventral Tegmental Area
Microinjections
Interpersonal Relations
Knockout Mice
Anxiety
Depression
Light

Keywords

  • anxiety
  • central amygdala
  • dopamine neurons
  • feeding
  • leptin receptor
  • ventral tegmental area

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Selective deletion of the leptin receptor in dopamine neurons produces anxiogenic-like behavior and increases dopaminergic activity in amygdala. / Liu, J.; Perez, S. M.; Zhang, W.; Lodge, D. J.; Lu, Xinyun.

In: Molecular Psychiatry, Vol. 16, No. 10, 01.10.2011, p. 1024-1038.

Research output: Contribution to journalArticle

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