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

Abstract

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.

Methods : Spontaneous activity of VTA of dopaminergic neurons was extracellularly recorded in brain slices obtained from HFD-fed mice.

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.

Discussion : HFD-induced obesity attenuates D₂ receptor-mediated inhibition and increases the excitability of non-leptin-active VTA of dopaminergic neurons.