Orexin-A Hyperphagia: Hindbrain Participation in Consummatory Feeding Responses
Orexin-A Hyperphagia: Hindbrain Participation in Consummatory Feeding Responses
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DOI：
10.1210/en.2008-0293
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发表时间：
2009-03-01
期刊：
影响因子：
4.8
通讯作者：
Grigg, Lindsay A.
中科院分区：
文献类型：
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作者：
Baird, John-Paul;Choe, Angela;Grigg, Lindsay A.
食欲素- a （ORXA）是一种由外侧下丘脑产生的促食神经肽，当注射到脑室或前脑核时，可增加食物摄入量。我们采用舔舐微结构分析的方法，评价完好和后脑损伤大鼠后脑和前脑ORXA的作用，以确定ORXA贪食的动机和解剖学基础。在第4脑室插管的完整大鼠（4V）接受载体（人工脑脊液）或ORXA（0.1, 0.4, 1或10 nM）注射，90分钟后给予0.1 M蔗糖。以双解离方式分别增加1 nM和10 nM剂量的饲料大小和频率。在实验2中，给大鼠提供不同热量和味觉强度的溶液（水和0.1和1 M蔗糖），给予4V 1 nM的ORXA。ORXA增加了所有试吃者的用餐频率。ORXA只增加了0.1 M蔗糖的餐量，通过延长用餐时间而不影响早期摄食率或舔爆大小，这表明4V ORXA影响的是抑止摄食后反馈，而不是味道评价。实验3，在第三脑室（3V）有套管的大鼠接受以后脑区为中心的髓背病变（APX组）或假手术，在1 nM 3V ORXA/人工脑脊液注射后，舔取水和0.1 M和1 M蔗糖。实验2中4V ORXA后观察到，3V ORXA使假手术组所有品尝者的蔗糖粒大小和用餐频率增加了0.1 M。在APX组，3V ORXA注射影响进餐频率，但不再增加进餐量。然而，APX大鼠在断食断水和注射3V血管紧张素II后，给糖0.1 M时食量增加。在3V注射黑素皮素-3/4受体激动剂melanotan II （1 nM）后，它们也显示出进餐大小的抑制。这些发现表明，单独束的后脑区和下核是增加对3V ORXA的终食反应（进食量）而非食欲反应（进食频率）所必需的。餐量增加可能是由于ORXA给后脑或前脑室引起的摄食后反馈抑制减少。（内分泌学150:1202-1216,2009）
Orexin-A (ORXA) is an orexigenic neuropeptide produced by the lateral hypothalamus that increases food intake when injected into the brain ventricles or forebrain nuclei. We used a licking microstructure analysis to evaluate hindbrain and forebrain ORXA effects in intact and hindbrain-lesioned rats, to identify the motivational and anatomical bases of ORXA hyperphagia. Intact rats with cannulas in the fourth brain ventricle (4V) received vehicle (artificial cerebrospinal fluid) or ORXA(0.1, 0.4, 1, or 10 nM) injections before 90 min access to 0.1 M sucrose. Meal size and frequency were increased in a double-dissociated manner by the 1 and 10 nM doses, respectively. In experiment 2, 4V 1 nM ORXA was applied to rats offered solutions varied in caloric and gustatory intensity (water and 0.1 and 1 M sucrose). ORXA increased meal frequency for all tastants. ORXA increased meal size only for 0.1 M sucrose, by prolonging the meal without affecting early ingestion rate or lick burst size, suggesting that 4V ORXA influenced inhibitory postingestive feedback rather than taste evaluation. In experiment 3, rats with cannulas in the third ventricle (3V) received dorsal medullary lesions centered on the area postrema (APX group) or sham procedures, and licking for water and 0.1 and 1 M sucrose was evaluated after 1 nM 3V ORXA/artificial cerebrospinal fluid injections. The 3V ORXA increased 0.1 M sucrose meal size and meal frequency for all tastants in the sham group, as observed after 4V ORXA in experiment 2. In the APX group, 3V ORXA injections influenced meal frequency, but they no longer increased meal size. However, the APX rats increased meal size for 0.1 M sucrose after food and water deprivation and after 3V angiotensin II injection. They also showed meal size suppression after 3V injection of the melanocortin-3/4 receptor agonist melanotan II (1 nM). These findings suggest that the area postrema and subjacent nucleus of the solitary tract are necessary for increases in consummatory (meal size) but not appetitive (meal frequency) responses to 3V ORXA. The meal size increases may be due to reduced postingestive feedback inhibition induced by ORXA delivered to either the hindbrain or forebrain ventricles. (Endocrinology 150: 1202-1216, 2009)