Orexin A in the VTA is critical for the induction of synaptic plasticity and Behavioral Sensitization to cocaine
Orexin A in the VTA is critical for the induction of synaptic plasticity and Behavioral Sensitization to cocaine
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DOI：
10.1016/j.neuron.2006.01.016
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发表时间：
2006-02-16
期刊：
影响因子：
16.2
通讯作者：
Bonci, A
中科院分区：
文献类型：
--
作者：
Borgland, SL;Taha, SA;Bonci, A
腹侧被盖区（VTA）的多巴胺神经元是成瘾性药物诱导的突触可塑性的关键部位。下丘脑外侧部含有食欲素/下丘脑泌素的神经元投射到腹侧被盖区，行为学研究表明食欲素神经元在动机、进食和适应行为中起重要作用。然而，食欲素信号在神经可塑性中的作用知之甚少。本研究表明，在体外应用的食欲素A诱导增强N-甲基-D-天冬氨酸受体（NMDAR）介导的神经传递通过PLC/PKC依赖性插入NMDARs腹侧被盖区多巴胺神经元突触。此外，食欲素1受体拮抗剂的体内给药阻断可卡因的运动敏化，并阻断VTA多巴胺神经元中可卡因诱导的兴奋性电流增强。这些结果提供了在体外和体内的证据食欲素信号在腹侧被盖区的神经可塑性相关成瘾的关键作用。
Dopamine neurons in the ventral tegmental area (VTA) represent a critical site of synaptic plasticity induced by addictive drugs. Orexin/hypocretin-containing neurons in the lateral hypothalamus project to the VTA, and behavioral studies have suggested that orexin neurons play an important role in motivation, feeding, and adaptive behaviors. However, the role of orexin signaling in neural plasticity is poorly understood. The present study shows that in vitro application of orexin A induces potentiation of N-methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission via a PLC/PKC-dependent insertion of NMDARs in VTA dopamine neuron synapses. Furthermore, in vivo administration of an orexin 1 receptor antagonist blocks locomotor sensitization to cocaine and occludes cocaine-induced potentiation of excitatory currents in VTA dopamine neurons. These results provide in vitro and in vivo evidence for a critical role of orexin signaling in the VTA in neural plasticity relevant to addiction.