Interaction between Leptin and Dopamine in the Food Reward System of Dopaminergic Neurons in High-fat Diet-induced Obesity

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  • Koyama Susumu
    Department of Advanced Pharmacology, Faculty of Pharmaceutical Sciences, Daiichi University of Pharmacy
  • Yamawaki Yosuke
    Department of Advanced Pharmacology, Faculty of Pharmaceutical Sciences, Daiichi University of Pharmacy
  • Yasukawa Keiji
    Department of Advanced Pharmacology, Faculty of Pharmaceutical Sciences, Daiichi University of Pharmacy

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  • 高脂肪食負荷肥満誘発における脳内食報酬系ドパミン神経のレプチンとドパミンの相互作用
  • コウシボウショク フカ ヒマン ユウハツ ニ オケル ノウナイショク ホウシュウケイ ドパミン シンケイ ノ レプチン ト ドパミン ノ ソウゴ サヨウ

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Abstract

<p>Objectives : Our previous study revealed the presence or absence of a leptin response in the ventral tegmental area (VTA) of dopaminergic neurons and the enhancement of the excitability of these neurons via dopamine in mice fed a high-fat diet (HFD). HFD-fed mice were divided into obesity-prone (Ob-P) and obesity-resistant (Ob-R) groups. In this study, we hypothesized that the excitability of VTA dopaminergic neurons might be augmented through the action of leptin/dopamine in Ob-P mice compared to that in Ob-R mice.</p><p>Methods : Spontaneous activity of VTA of dopaminergic neurons was extracellularly recorded in brain slices obtained from HFD-fed mice.</p><p>Results : Leptin-responsive and non-leptin-responsive neurons were observed in HFD-fed mice. In Ob-P mice, the inhibition of spontaneous activity by quinpirole (a D2 receptor agonist) in non-leptin-responsive neurons was significantly lower than that in leptin-responsive neurons. No differences were observed in Ob-R mice.</p><p>Discussion : HFD-induced obesity attenuates D2 receptor-mediated inhibition and increases the excitability of non-leptin-active VTA of dopaminergic neurons.</p>

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