Orexin A/hypocretin-1 selectively promotes motivation for positive reinforcers.
Orexin A/hypocretin-1 selectively promotes motivation for positive reinforcers.
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DOI：
10.1523/jneurosci.6096-08.2009
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发表时间：
2009-09-09
期刊：
影响因子：
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通讯作者：
Bonci A
中科院分区：
文献类型：
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作者：
Borgland SL;Chang SJ;Bowers MS;Thompson JL;Vittoz N;Floresco SB;Chou J;Chen BT;Bonci A
食欲素A/下丘脑分泌素-1 （oxA/hcrt-1）被认为是多巴胺依赖性神经元活动和行为的调节剂。然而，这个系统在驱动动机行为中的作用仍然知之甚少。在这里，我们发现食欲素/下丘脑分泌素受体-1 （ox/hcrt-1R）信号对于高度显著的正强化的动机很重要。阻断ox/hcrt-1R选择性地减少了自我管理可卡因或高脂肪食物颗粒的工作。此外，oxA/hcrt-1仅在可卡因或高脂肪自我给药的大鼠中增强了对腹侧被盖区（VTA）的突触前谷氨酸能输入。最后，oxA/hcrt-1介导的兴奋性突触传递到VTA神经元后，在令人兴奋的、厌恶的刺激下没有增强，这表明oxA/hcrt-1介导的谷氨酸能突触传递被高度显著的正强化物选择性地增强。这些实验为oxA/hcrt-1信号在高度显著强化物的动机中的选择性作用提供了证据，并可能代表了设计新疗法的独特机会，该疗法可以选择性地减少过度驱动以消耗高度显著性的正强化物。
Orexin A/hypocretin-1 (oxA/hcrt-1) is known to be a modulator of dopamine-dependent neuronal activity and behaviors. However, the role of this system in driving motivated behaviors remains poorly understood. Here, we show that orexin/hypocretin receptor-1 (ox/hcrt-1R) signaling is important for motivation for highly salient, positive reinforcement. Blockade of ox/hcrt-1R selectively reduced work to self-administer cocaine or high fat food pellets. Moreover, oxA/hcrt-1 strengthened presynaptic glutamatergic inputs to the ventral tegmental area (VTA) only in cocaine or high fat self-administering rats. Finally, oxA/hcrt-1-mediated excitatory synaptic transmission onto VTA neurons was not potentiated following an arousing, aversive stimulus, suggesting that oxA/hcrt-1-mediated glutamatergic synaptic transmission was potentiated selectively with highly salient positive reinforcers. These experiments provide evidence for a selective role of oxA/hcrt-1 signaling in motivation for highly salient reinforcers and may represent a unique opportunity to design novel therapies that selectively reduce excessive drive to consume positive reinforcers of high salience.