title: Leptin/LepRb in the Ventral Tegmental Area Mediates Anxiety-Related Behaviors.
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 Lepr(flox/flox) 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. Lepr(flox/flox) 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 findings suggest that leptin-LepRb signaling in the ventral tegmental area plays an important role in the regulation of anxiety-related behaviors.
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX (Drs Liu, Guo, and Lu); Institute for Metabolic and Neuropsychiatric Disorders, Binzhou Medical University, Binzhou, China (Dr Guo).
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX (Drs Liu, Guo, and Lu); Institute for Metabolic and Neuropsychiatric Disorders, Binzhou Medical University, Binzhou, China (Dr Guo).
authors.forename: Ming
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX (Drs Liu, Guo, and Lu); Institute for Metabolic and Neuropsychiatric Disorders, Binzhou Medical University, Binzhou, China (Dr Guo). lux3@uthscsa.edu.
authors.forename: Xin-Yun
authors.initials: XY
authors.lastname: Lu
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D057967:Infusions, Intraventricular; D020738:Leptin / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054411:Receptors, Leptin / Q000819:agonists* / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
chemical_list: D020738:Leptin; D054411:Receptors, Leptin
keywords: JAK2/STAT3; Leptin receptor; elevated plus-maze test; light-dark box; novelty suppessed feeding