Dataset Information

The 5-HT_2C receptor agonist meta-chlorophenylpiperazine (mCPP) reduces palatable food consumption and BOLD fMRI responses to food images in healthy female volunteers.

ABSTRACT:

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.

SUBMITTER: Thomas JM

PROVIDER: S-EPMC5748416 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Thomas Jason M JM Dourish Colin T CT Tomlinson Jeremy J Hassan-Smith Zaki Z Hansen Peter C PC Higgs Suzanne S

Psychopharmacology 20171028 1

<h4>Rationale</h4>Brain 5-HT<sub>2C</sub> receptors form part of a neural network that controls eating behaviour. 5-HT<sub>2C</sub> 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<sub>2C</sub> 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<sub ...[more]

PMID: 29080906

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Project description:BackgroundEmerging data suggest that weight gain is associated with changes in neural response to palatable food tastes and palatable food cues, which may serve to maintain overeating.ObjectiveWe investigated whether weight gain is associated with neural changes in response to tastes of milkshakes varying in fat and sugar content and palatable food images.MethodsWe compared changes in neural activity between initially healthy-weight adolescents who gained weight (n = 36) and those showing weight stability (n = 31) over 2-3 y.ResultsAdolescents who gained weight compared with those who remained weight stable showed decreases in activation in the postcentral gyrus, prefrontal cortex, insula, and anterior cingulate cortex, and increases in activation in the parietal lobe, posterior cingulate cortex, and inferior frontal gyrus in response to a high-fat/low-sugar compared with low-fat/low-sugar milkshake. Weight gainers also showed greater decreases in activation in the anterior insula and lateral orbitofrontal cortex in response to a high-fat/high-sugar compared with low-fat/low-sugar milkshake than those who remained weight stable. No group differences emerged in response to a low-fat/high-sugar compared with a low-fat/low-sugar milkshake. Weight gainers compared with those who remained weight stable showed greater decreases in activation in the middle temporal gyrus and increases in cuneus activation in response to appetizing compared with unappetizing food pictures. The significant interactions were partially driven by group differences in baseline responsivity and by opposite changes in neural activation in adolescents who remained weight stable.ConclusionsData suggest that weight gain is associated with a decrease in responsivity of regions associated with taste and reward processing to palatable high-fat- and high-fat/high-sugar food tastes. Data also suggest that avoiding weight gain increases taste sensitivity, which may prevent future excessive weight gain.This trial was registered at clinicaltrials.gov as NCT01949636.

Dataset Information

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

Objectives

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Rationale

Objectives

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

The 5-HT_2C receptor agonist meta-chlorophenylpiperazine (mCPP) reduces palatable food consumption and BOLD fMRI responses to food images in healthy female volunteers.