Neuron
Volume 51, Issue 6, 21 September 2006, Pages 811-822
Journal home page for Neuron

Article
Leptin Regulation of the Mesoaccumbens Dopamine Pathway

https://doi.org/10.1016/j.neuron.2006.09.006Get rights and content
Under an Elsevier user license
open archive

Summary

Leptin is an adipose-derived hormone that acts on hypothalamic leptin receptors to regulate energy balance. Leptin receptors are also expressed in extrahypothalamic sites including the ventral tegmental area (VTA), critical to brain reward circuitry. We report that leptin targets DA and GABA neurons of the VTA, inducing phosphorylation of signal-transducer-and-activator-of-transcription-3 (STAT3). Retrograde tracing combined with pSTAT3 immunohistochemistry show leptin-responsive VTA neurons projecting to nucleus accumbens (NAc). Assessing leptin function in the VTA, we showed that ob/ob mice had diminished locomotor response to amphetamine and lacked locomotor sensitization to repeated amphetamine injections, both defects reversed by leptin infusion. Electrically stimulated DA release from NAc shell terminals was markedly reduced in ob/ob slice preparations, and NAc DA levels and TH expression were lower. These data define a role for leptin in mesoaccumbens DA signaling and indicate that the mesoaccumbens DA pathway, critical to integrating motivated behavior, responds to this adipose-derived signal.

MOLNEURO
HUMDISEASE

Cited by (0)

3

Present address: Department of Pharmacology, Center for Research in Neurological Sciences, Université de Montréal, Roger-Gaudry Building, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada.