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 nmol/L) directly inhibited spontaneous firing in 71% of putative VTA dopaminergic neurons (leptin‐responsive), whereas the remaining 29% of neurons were leptin‐nonresponsive. In 41% of leptin‐responsive neurons, leptin attenuated the reduced firing rate produced by quinpirole (100 nmol/L), whereas the remaining 59% of neurons exhibited no effect of leptin. In leptin‐nonresponsive 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, whereas 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 the development of obesity.
Highlights
Obesity is one of the most important public health issues in modern society
We report two leptin receptor-mediated effects on putative ventral tegmental area (VTA) dopaminergic neurons
We show that leptin directly reduces spontaneous firing rate in 71% of putative VTA dopaminergic neurons
Summary
Obesity is one of the most important public health issues in modern society. It is a risk factor for metabolic syndrome, impaired glucose tolerance, and type 2 diabetes mellitus. Leptin is critical for regulation of energy intake and expenditure, and contributes to food reward through the mesolimbic dopaminergic system (Hommel et al 2006; Domingos et al 2011). Histochemical studies have shown that functioning leptin receptors are expressed in a subpopulation of ventral tegmental area (VTA) dopaminergic neurons (Figlewicz et al 2003; Fulton et al 2006; Hommel et al 2006; Scott et al 2009; Leshan et al 2010)
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