School of Psychology, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Department of Psychology, Aston University, Birmingham, B4 7ET, UK.
Psychopharmacology (Berl). 2018 Jan;235(1):257-267. doi: 10.1007/s00213-017-4764-9. Epub 2017 Oct 28.
Brain 5-HT receptors form part of a neural network that controls eating behaviour. 5-HT receptor agonists decrease food intake by activating proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus, but recent research in rodents has suggested that 5-HT receptor agonists may also act via dopaminergic circuitry to reduce the rewarding value of food and other reinforcers. No mechanistic studies on the effects of 5-HT agonists on food intake in humans have been conducted to date.
The present study examined the effects of the 5-HT receptor agonist meta-chlorophenylpiperazine (mCPP) on food consumption, eating microstructure and blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to food pictures in healthy female volunteers.
In a double-blind, placebo-controlled, crossover design, participants were randomized immediately after screening to receive oral mCPP (30mg) in a single morning dose, or placebo, in a counterbalanced order. Test foods were served from a Universal Eating Monitor (UEM) that measured eating rate and fMRI BOLD signals to the sight of food and non-food images were recorded.
mCPP decreased rated appetite and intake of a palatable snack eaten in the absence of hunger but had no significant effect on the consumption of a pasta lunch (although pasta eating rate was reduced). mCPP also decreased BOLD fMRI responses to the sight of food pictures in areas of reward-associated circuitry. A post hoc analysis identified individual variability in the response to mCPP (exploratory responder-non-responder analysis). Some participants did not reduce their cookie intake after treatment with mCPP and this lack of response was associated with enhanced ratings of cookie pleasantness and enhanced baseline BOLD responses to food images in key reward and appetite circuitry.
These results suggest that 5-HT receptor activation in humans inhibits food reward-related responding and that further investigation of stratification of responding to mCPP and other 5-HT receptor agonists is warranted.
大脑 5-HT 受体构成了控制进食行为的神经网络的一部分。5-HT 受体激动剂通过激活下丘脑弓状核中的 proopiomelanocortin（POMC）神经元来减少食物摄入，但最近在啮齿动物中的研究表明，5-HT 受体激动剂也可能通过多巴胺能回路起作用，从而降低食物和其他强化物的奖赏价值。迄今为止，尚未对 5-HT 激动剂对人类食物摄入的影响进行机制研究。
本研究旨在探讨 5-HT 受体激动剂 meta-氯苯哌嗪（mCPP）对健康女性志愿者的食物摄入量、进食微观结构和食物图片的血氧水平依赖性（BOLD）功能磁共振成像（fMRI）反应的影响。
在一项双盲、安慰剂对照、交叉设计中，参与者在筛选后立即随机分为两组，分别在一个早晨口服 mCPP（30mg）或安慰剂，以平衡顺序给药。测试食物由通用进食监测仪（UEM）提供，该仪器可测量进食速度，记录食物和非食物图像的 fMRI BOLD 信号。
mCPP 降低了食欲评分和在饥饿状态下食用的美味小吃的摄入量，但对意大利面午餐的摄入量没有显著影响（尽管意大利面的进食速度有所降低）。mCPP 还降低了与奖赏相关回路中食物图片视觉刺激的 fMRI BOLD 反应。事后分析确定了对 mCPP 反应的个体差异（探索性应答者-无应答者分析）。一些参与者在接受 mCPP 治疗后没有减少饼干摄入量，这种无反应与饼干愉悦感评分的增加以及关键奖赏和食欲回路中食物图像的基线 BOLD 反应的增加有关。
这些结果表明，5-HT 受体在人类中的激活抑制了与食物奖赏相关的反应，进一步研究 mCPP 和其他 5-HT 受体激动剂的反应分层是必要的。
