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Leptin attenuates D(2) receptor‐mediated inhibition of putative ventral tegmental area dopaminergic neurons
Obesity causes hyperleptinemia. We have previously shown that D(2) 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 D...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880875/ https://www.ncbi.nlm.nih.gov/pubmed/29611323 http://dx.doi.org/10.14814/phy2.13631 |
Sumario: | Obesity causes hyperleptinemia. We have previously shown that D(2) 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 D(2) receptor‐mediated effects on VTA dopaminergic neurons. To investigate our hypothesis, we examined leptin effects on D(2) 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 D(2) 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. |
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