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

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 (LeprDAT-Cre). These mice exhibit normal body weight and feeding. Behaviorally, LeprDAT-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 LeprDAT-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 LeprDAT-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.

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Acknowledgements

This work was supported by NIH grants NIMH 076929 and NIMH 073844 (to XYL), an NARSAD award from the Maltz Family Foundation (to DJL) and an NIH grant NS056237 (to WZ). We thank Dr Streamson Chua for the Leprflox/flox mice, Dr Xiaoxi Zhuang for the Slc6a3-Cre mice.

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Liu, J., Perez, S., Zhang, W. et al. Selective deletion of the leptin receptor in dopamine neurons produces anxiogenic-like behavior and increases dopaminergic activity in amygdala. Mol Psychiatry 16, 1024–1038 (2011). https://doi.org/10.1038/mp.2011.36

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