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Int J Neuropsychopharmacol. 2015 Oct 5;19(2). pii: pyv115. doi: 10.1093/ijnp/pyv115.

Leptin/LepRb in the Ventral Tegmental Area Mediates Anxiety-Related Behaviors.

Author information

1
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).
2
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.

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.

KEYWORDS:

JAK2/STAT3; Leptin receptor; elevated plus-maze test; light-dark box; novelty suppessed feeding

PMID:
26438799
PMCID:
PMC4772826
DOI:
10.1093/ijnp/pyv115
[Indexed for MEDLINE]
Free PMC Article

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