Adiponectin modulates ventral tegmental area dopamine neuron activity and anxiety-related behavior through AdipoR1

Fengjiao Sun, Yun Lei, Jingjing You, Linshan Sun, Jacob Garza, Di Zhang, Ming Guo, Phillip E. Scherer, Daniel Lodge, Xin Yun Lu

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Adiponectin, a metabolic hormone secreted by adipocytes, can cross the blood–brain barrier to act on neurons in different brain regions, including those involved in stress-related disorders. Here we show that dopamine neurons in the ventral tegmental area (VTA) express adiponectin receptor 1 (AdipoR1). Intra-VTA infusion of adiponectin or the adiponectin mimetic AdipoRon in wild-type mice decreases basal dopamine neuron population activity and firing rate and reverses the restraint stress-induced increase in dopamine neuron activity and anxiety behavior. Adiponectin haploinsufficiency leads to increased dopamine neuron firing and anxiety behavior under basal conditions. Ablation of AdipoR1 specifically from dopamine neurons enhances neuronal and anxiogenic responses to restraint stress. The effects of intra-VTA infusion of adiponectin on neuronal activity and behavior were abolished in mice lacking AdipoR1 in dopamine neurons. These observations indicate that adiponectin can directly modulate VTA dopamine neuron activity and anxiety behavior, and that AdipoR1 is required for adiponectin-induced inhibition of dopamine neurons and anxiolytic effects. These results strengthen the idea of adiponectin as a key biological factor that links metabolic syndrome and emotional disorders.

Original languageEnglish (US)
Pages (from-to)126-144
Number of pages19
JournalMolecular Psychiatry
Issue number1
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Molecular Biology


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