Department of Neurosciences, Medical University of South Carolina, Basic Science Building 403, 173 Ashley Avenue, MSC 510, Charleston, SC 29425, USA.
Physiol Behav. 2010 Jul 14;100(5):419-28. doi: 10.1016/j.physbeh.2010.03.009. Epub 2010 Mar 23.
Orexins (also named hypocretins) are recently discovered neuropeptides made exclusively in the hypothalamus. Recent studies have shown that orexin cells located specifically in lateral hypothalamus (LH) are involved in motivated behavior for drugs of abuse as well as natural rewards. Administration of orexin has been shown to stimulate food consumption, and orexin signaling in VTA has been implicated in intake of high-fat food. In self-administration studies, the orexin 1 receptor antagonist SB-334867 (SB) attenuated operant responding for high-fat pellets, sucrose pellets and ethanol, but not cocaine, demonstrating that signaling at orexin receptors is necessary for reinforcement of specific rewards. The orexin system is also implicated in associations between rewards and relevant stimuli. For example, Fos expression in LH orexin neurons varied in proportion to conditioned place preference (CPP) for food, morphine, or cocaine. This Fos expression was altered accordingly for CPP administered during protracted abstinence from morphine or cocaine, when preference for natural rewards was decreased and drug preference was increased. Additionally, orexin has been shown to be involved in reward-stimulus associations in the self-administration paradigm, where SB attenuated cue-induced reinstatement of extinguished sucrose- or cocaine-seeking. Although the specific circuitry mediating the effects of orexin on food reward remains unknown, VTA seems likely to be a critical target for at least some of these orexin actions. Thus, recent studies have established a role for orexin in reward-based feeding, and further investigation is warranted for determining whether function/dysfunction of the orexin system may contribute to the overeating associated with obesity. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.
食欲素（也称为下丘脑泌素）是最近发现的一种仅在下丘脑产生的神经肽。最近的研究表明，位于外侧下丘脑（LH）的食欲素细胞参与了滥用药物以及天然奖赏的动机行为。给予食欲素已被证明可刺激食物摄入，而 VTA 中的食欲素信号与高脂肪食物的摄入有关。在自我给药研究中，食欲素 1 受体拮抗剂 SB-334867（SB）减弱了高脂肪丸、蔗糖丸和乙醇的操作性反应，但对可卡因没有影响，这表明食欲素受体的信号传导对于特定奖赏的强化是必要的。食欲素系统还与奖赏和相关刺激之间的关联有关。例如，LH 食欲素神经元中的 Fos 表达与食物、吗啡或可卡因的条件性位置偏好（CPP）成正比。这种 Fos 表达相应地改变了吗啡或可卡因延长戒断期间 CPP 的表达，此时天然奖赏的偏好减少，药物偏好增加。此外，食欲素已被证明参与了自我给药范式中的奖赏-刺激关联，其中 SB 减弱了消退的蔗糖或可卡因寻求中的线索诱导的复燃。虽然介导食欲素对食物奖赏影响的特定回路尚不清楚，但 VTA 似乎很可能是这些食欲素作用的至少一些关键靶点。因此，最近的研究确立了食欲素在基于奖赏的进食中的作用，进一步的研究需要确定食欲素系统的功能/失调是否可能导致与肥胖相关的过度进食。本文是在 2009 年 7 月波特兰举行的摄食行为学会（SSIB）年会上，作为专题讨论、获奖者或主题演讲邀请的综述。
