The 5-HT(2C) receptor agonist meta-chlorophenylpiperazine (mCPP) reduces palatable food consumption and BOLD fMRI responses to food images in healthy female volunteers

RATIONALE: Brain 5-HT(2C) receptors form part of a neural network that controls eating behaviour. 5-HT(2C) 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(2C) 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(2C) agonists on food intake in humans have been conducted to date. OBJECTIVES: The present study examined the effects of the 5-HT(2C) 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These results suggest that 5-HT(2C) receptor activation in humans inhibits food reward-related responding and that further investigation of stratification of responding to mCPP and other 5-HT(2C) receptor agonists is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00213-017-4764-9) contains supplementary material, which is available to authorized users.