Dataset for: Leptin attenuates D2 receptor-mediated inhibition of putative ventral tegmental area dopaminergic neurons

Abstract

Obesity causes hyperleptinemia. We have previously shown that D2 receptor-mediated inhibition of ventral tegmental area (VTA) dopaminergic neurons is attenuated in diet-induced mice with obesity. Consequently, we hypothesized that high concentrations of serum leptin during obesity might modulate D2 receptor-mediated effects on VTA dopaminergic neurons. To investigate our hypothesis, we examined leptin effects on D2 receptor-mediated inhibition of putative VTA dopaminergic neurons from lean mice using electrophysiological techniques. Leptin (100 nM) directly inhibited spontaneous firing in 71% of putative VTA dopaminergic neurons (leptin-responsive), while the remaining 29% of neurons were leptin-non-responsive. In 41% of leptin-responsive neurons, leptin attenuated the reduced firing rate produced by quinpirole (100 nM), while the remaining 59% of neurons exhibited no effect of leptin. In leptin-non-responsive neurons, no significant leptin-induced effect was observed on reduced firing rate produced by quinpirole. In leptin-responsive neurons with positive leptin-induced attenuation of quinpirole effects, leptin-induced attenuation persisted for > 20 min, while no such persistent attenuation was observed in other types of neurons. In conclusion, leptin attenuates D2 receptor-mediated inhibition in a subpopulation of putative VTA dopaminergic neurons. We suggest that leptin directly decreases, and indirectly increases, excitability of VTA dopaminergic neurons. In turn, this may contribute to a change in feeding behavior through the mesolimbic dopaminergic system during development of obesity.