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Leptin: a potential anxiolytic by facilitation of fear extinction.
CNS Neurosci Ther. 2015 May; 21(5):425-34.CN

Abstract

AIMS

Anxiety disorders are characterized by a deficient extinction of fear memory. Evidence is growing that leptin influences numerous neuronal functions. The aims of this study were to investigate the effects and the mechanism of leptin on fear extinction.

METHODS AND RESULTS

Leptin (1 mg/kg, i.p) was applied to evaluate the anxiolytic effect in rat behavioral tests. Field potentials recording were used to investigate the changes in synaptic transmission in the thalamic-lateral amygadala (LA) pathway of rat. We found that leptin produced strong anxiolytic effects under basal condition and after acute stress. Systemic administration and intra-LA infusions of leptin facilitated extinction of conditioned fear responses. The antagonist of NMDA receptor, MK-801, blocked the effect of leptin on fear extinction completely. Furthermore, these effects of leptin on fear extinction were accompanied by a reversal of conditioning-induced synaptic potentiation in the LA. Leptin facilitated NMDA receptor-mediated synaptic transmission, and reversed amygdala long-term potentiation (LTP) in a dose-dependent manner in vitro, and this LTP depotentiation effect was mediated by NMDA receptor and MAPK signaling pathway.

CONCLUSIONS

These results identify a key role of leptin in dampening fear conditioning-induced synaptic potentiation in the LA through NMDA receptor and indicate a new strategy for treating anxiety disorders.

Links

PMC Free PDF

Authors+Show Affiliations

Wang W
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Liu SL
No affiliation info available
Li K
No affiliation info available
Chen Y
No affiliation info available
Jiang B
No affiliation info available
Li YK
No affiliation info available
Xiao JL
No affiliation info available
Yang S
No affiliation info available
Chen T
No affiliation info available
Chen JG
No affiliation info available
Li JG
No affiliation info available
Wang F
No affiliation info available

MeSH

AnimalsAnti-Anxiety AgentsAnxietyBasolateral Nuclear ComplexConditioning, PsychologicalDizocilpine MaleateDose-Response Relationship, DrugExcitatory Amino Acid AntagonistsExtinction, PsychologicalFearLeptinLong-Term PotentiationMice, Inbred C57BLNeural PathwaysRandom AllocationReceptors, N-Methyl-D-AspartateRecombinant ProteinsSynaptic TransmissionThalamusTissue Culture Techniques

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25645604

Citation

Wang, Wei, et al. "Leptin: a Potential Anxiolytic By Facilitation of Fear Extinction." CNS Neuroscience & Therapeutics, vol. 21, no. 5, 2015, pp. 425-34.
Wang W, Liu SL, Li K, et al. Leptin: a potential anxiolytic by facilitation of fear extinction. CNS Neurosci Ther. 2015;21(5):425-34.
Wang, W., Liu, S. L., Li, K., Chen, Y., Jiang, B., Li, Y. K., Xiao, J. L., Yang, S., Chen, T., Chen, J. G., Li, J. G., & Wang, F. (2015). Leptin: a potential anxiolytic by facilitation of fear extinction. CNS Neuroscience & Therapeutics, 21(5), 425-34. https://doi.org/10.1111/cns.12375
Wang W, et al. Leptin: a Potential Anxiolytic By Facilitation of Fear Extinction. CNS Neurosci Ther. 2015;21(5):425-34. PubMed PMID: 25645604.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Leptin: a potential anxiolytic by facilitation of fear extinction. AU - Wang,Wei, AU - Liu,Song-Lin, AU - Li,Kuan, AU - Chen,Yu, AU - Jiang,Bo, AU - Li,Yan-Kun, AU - Xiao,Jun-Li, AU - Yang,Si, AU - Chen,Tao, AU - Chen,Jian-Guo, AU - Li,Jia-Geng, AU - Wang,Fang, Y1 - 2015/01/29/ PY - 2014/05/16/received PY - 2014/11/26/revised PY - 2014/12/08/accepted PY - 2015/2/4/entrez PY - 2015/2/4/pubmed PY - 2016/1/16/medline KW - Amygdala KW - Anxiety KW - Fear conditioning KW - Leptin KW - Long-term potentiation SP - 425 EP - 34 JF - CNS neuroscience & therapeutics JO - CNS Neurosci Ther VL - 21 IS - 5 N2 - AIMS: Anxiety disorders are characterized by a deficient extinction of fear memory. Evidence is growing that leptin influences numerous neuronal functions. The aims of this study were to investigate the effects and the mechanism of leptin on fear extinction. METHODS AND RESULTS: Leptin (1 mg/kg, i.p) was applied to evaluate the anxiolytic effect in rat behavioral tests. Field potentials recording were used to investigate the changes in synaptic transmission in the thalamic-lateral amygadala (LA) pathway of rat. We found that leptin produced strong anxiolytic effects under basal condition and after acute stress. Systemic administration and intra-LA infusions of leptin facilitated extinction of conditioned fear responses. The antagonist of NMDA receptor, MK-801, blocked the effect of leptin on fear extinction completely. Furthermore, these effects of leptin on fear extinction were accompanied by a reversal of conditioning-induced synaptic potentiation in the LA. Leptin facilitated NMDA receptor-mediated synaptic transmission, and reversed amygdala long-term potentiation (LTP) in a dose-dependent manner in vitro, and this LTP depotentiation effect was mediated by NMDA receptor and MAPK signaling pathway. CONCLUSIONS: These results identify a key role of leptin in dampening fear conditioning-induced synaptic potentiation in the LA through NMDA receptor and indicate a new strategy for treating anxiety disorders. SN - 1755-5949 UR - https://www.unboundmedicine.com/medline/citation/25645604/Leptin:_a_potential_anxiolytic_by_facilitation_of_fear_extinction_ DB - PRIME DP - Unbound Medicine ER -