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

Mol Psychiatry. 2011 Oct;16(10):1024-38. doi: 10.1038/mp.2011.36. Epub 2011 Apr 12.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Amygdala / cytology
  • Amygdala / physiology*
  • Animals
  • Anxiety / metabolism*
  • Dopamine / metabolism
  • Dopaminergic Neurons / physiology*
  • Exploratory Behavior / physiology*
  • Interpersonal Relations
  • Maze Learning / physiology
  • Mice
  • Mice, Knockout
  • Receptors, Leptin / genetics
  • Receptors, Leptin / physiology*
  • Signal Transduction / physiology
  • Ventral Tegmental Area / cytology
  • Ventral Tegmental Area / physiology


  • Receptors, Leptin
  • Dopamine