Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Addict Biol. 2017 Nov;22(6):1695-1705. doi: 10.1111/adb.12432. Epub 2016 Aug 2.
The hypocretin/orexin (HCRT) system is implicated in reward and reinforcement processes through actions on the mesolimbic dopamine (DA) system. Here we provide evidence for the relationship between HCRT and DA in vivo in anesthetized and freely moving mice. The ability of cocaine to elicit reward-related behaviors in mice lacking the HCRT prepro-peptide (HCRT knock-out; KO) and wild-type controls was determined using conditioned place preference. Using a combination of microdialysis and in vivo fast scan cyclic voltammetry in anesthetized and freely moving mice, we investigated the underlying role of HCRT in the regulation of DA release and uptake. We show that, unlike wild-type mice, HCRT KO mice fail to develop characteristic conditioned place preference for cocaine. These mice also demonstrated reduced DA release and uptake under baseline conditions in both anesthetized and freely moving experiments. Further, diminished DA signaling in HCRT KO mice persists following administration of cocaine. These findings indicate that HCRT is essential for the expression of behaviors associated with the rewarding effects of cocaine, and suggest that HCRT regulation of reward and reinforcement may be related to disruptions to DA neurotransmission.
下丘脑泌素/食欲素（HCRT）系统通过对中脑边缘多巴胺（DA）系统的作用而与奖赏和强化过程有关。在这里，我们在麻醉和自由活动的小鼠中提供了 HCRT 与 DA 之间体内关系的证据。使用条件性位置偏爱，确定了缺乏 HCRT 前肽（HCRT 敲除；KO）和野生型对照的小鼠中可卡因引起奖赏相关行为的能力。通过组合使用麻醉和自由活动的小鼠中的微透析和体内快速扫描循环伏安法，我们研究了 HCRT 在调节 DA 释放和摄取中的潜在作用。我们表明，与野生型小鼠不同，HCRT KO 小鼠未能对可卡因产生特征性条件性位置偏好。这些小鼠在麻醉和自由活动实验中基础条件下也表现出 DA 释放和摄取减少。此外，在给予可卡因后，HCRT KO 小鼠中的 DA 信号仍然减弱。这些发现表明 HCRT 对于与可卡因奖赏作用相关的行为表达是必不可少的，并且表明 HCRT 对奖赏和强化的调节可能与 DA 神经传递的中断有关。
