Department of Psychology, University of Pennsylvania, 433 S. University Avenue, Rm. 327, Philadelphia, PA, 19104, USA.
Psychopharmacology (Berl). 2018 Aug;235(8):2287-2301. doi: 10.1007/s00213-018-4925-5. Epub 2018 May 23.
Prolactin-releasing peptide (PrRP) is a neuropeptide that suppresses food intake and increases body temperature when delivered to the forebrain ventricularly or parenchymally. However, PrRP's receptor GPR10 is widely distributed throughout the brain with particularly high levels found in the dorsomedial hindbrain. Thus, we hypothesized that hindbrain-directed PrRP administration would affect energy balance and motivated feeding behavior.
To address this hypothesis, a range of behavioral and physiologic variables were measured in Sprague-Dawley rats that received PrRP delivered to the fourth ventricle (4V) or the nucleus of the solitary tract (NTS) at the level of the area postrema (AP).
4V PrRP delivery decreased chow intake and body weight, in part, through decreasing meal size in ad libitum maintained rats tested at dark onset. PrRP inhibited feeding when delivered to the nucleus tractus solitarius (NTS), but not to more ventral hindbrain structures. In addition, 4V as well as direct NTS administration of PrRP increased core temperature. By contrast, 4V PrRP did not reduce ad libitum intake of highly palatable food or the motivation to work for or seek palatable foods.
The dorsomedial hindbrain and NTS/AP, in particular, are sites of action in PrRP/GPR10-mediated control of chow intake, core temperature, and body weight.
催乳素释放肽(PrRP)是一种神经肽,当它被递送至前脑脑室或实质内时,会抑制食物摄入并升高体温。然而,PrRP 的受体 GPR10 广泛分布于整个大脑,在背内侧后脑尤其高。因此,我们假设脑定向 PrRP 给药会影响能量平衡和摄食动机行为。
为了验证这一假设,我们在 Sprague-Dawley 大鼠中测量了一系列行为和生理变量,这些大鼠接受了递送至第四脑室(4V)或孤束核(NTS)的 PrRP 给药,给药部位位于后穹窿(AP)水平。
4V PrRP 给药减少了大鼠的随意进食量和体重,部分原因是在黑暗开始时检测到的自由进食大鼠中减少了每餐的大小。当 PrRP 被递送至孤束核(NTS)时,它会抑制进食,但不会递送至更腹侧的后脑结构。此外,4V 以及直接 NTS 给药的 PrRP 会升高核心体温。相比之下,4V PrRP 并没有减少对高适口性食物的随意摄入,也没有减少对适口性食物的工作或寻求动力。
背内侧后脑和 NTS/AP,特别是,是 PrRP/GPR10 介导的控制摄食量、核心体温和体重的作用部位。