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Psychopharmacology (Berl). 2018 Jan;235(1):257-267. doi: 10.1007/s00213-017-4764-9. Epub 2017 Oct 28.

The 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) reduces palatable food consumption and BOLD fMRI responses to food images in healthy female volunteers.

Author information

1
School of Psychology, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
2
Department of Psychology, Aston University, Birmingham, B4 7ET, UK.
3
P1vital, Manor House, Howbery Park, Wallingford, Oxfordshire, OX10 8BA, UK.
4
Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford NIHR Biomedical Research Centre, Churchill Hospital, University of Oxford, Headington, OX7 3LJ, UK.
5
Centre for Endocrinology, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, B15 2TH, UK.
6
School of Psychology, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. s.higgs.1@bham.ac.uk.

Abstract

RATIONALE:

Brain 5-HT2C receptors form part of a neural network that controls eating behaviour. 5-HT2C 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-HT2C 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-HT2C agonists on food intake in humans have been conducted to date.

OBJECTIVES:

The present study examined the effects of the 5-HT2C 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-HT2C receptor activation in humans inhibits food reward-related responding and that further investigation of stratification of responding to mCPP and other 5-HT2C receptor agonists is warranted.

KEYWORDS:

5-HT2C; BOLD fMRI; Food consumption

PMID:
29080906
PMCID:
PMC5748416
DOI:
10.1007/s00213-017-4764-9
[Indexed for MEDLINE]
Free PMC Article

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