Leptin attenuates D(2) receptor-mediated inhibition of putative ventral tegmental area dopaminergic neurons.
Leptin attenuates D(2) receptor-mediated inhibition of putative ventral tegmental area dopaminergic neurons.
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DOI：
10.14814/phy2.13631
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发表时间：
2018-04
影响因子：
2.5
通讯作者：
Koyama S
中科院分区：
文献类型：
--
作者：
Murakami T;Enjoji M;Koyama S
肥胖导致高瘦素血症。我们之前的研究表明，D2受体介导的腹侧被盖区（VTA）多巴胺能神经元的抑制在饮食诱导的肥胖小鼠中减弱。因此，我们假设肥胖期间高浓度的血清瘦素可能调节D2受体介导的VTA多巴胺能神经元的作用。为了验证我们的假设，我们使用电生理技术检测了瘦素对D2受体介导的VTA多巴胺能神经元抑制的影响。瘦素（100 nmol/L）直接抑制71%的VTA多巴胺能神经元（瘦素反应）的自发放电，而其余29%的神经元是瘦素无反应的。在41%的瘦素反应神经元中，瘦素减弱了喹匹罗（100 nmol/L）引起的放电速率降低，而其余59%的神经元没有表现出瘦素的作用。在瘦素无反应的神经元中，未观察到瘦素诱导的对喹匹罗降低放电速率的作用。在瘦素反应神经元中，瘦素诱导的喹匹罗效应衰减呈阳性，瘦素诱导的衰减持续了大约20分钟，而在其他类型的神经元中没有观察到这种持续衰减。总之，瘦素减弱了D2受体介导的VTA多巴胺能神经元亚群的抑制作用。我们认为瘦素直接降低或间接增加VTA多巴胺能神经元的兴奋性。反过来，这可能有助于在肥胖发展过程中通过中脑边缘多巴胺能系统改变摄食行为。
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.