studying-food-reward-and-motivation-in-humans

Studying Food Reward and Motivation in Humans

A key challenge in studying reward processing in humans is to go beyond subjective self-report measures and quantify different aspects of reward such as ...

University of Cambridge

There has been a resurgence of interest in the field of reward processing in schizophrenia in recent years, aided by insights from functional neuroimaging. We examine how disturbances in reward-related processes relate to the pathophysiology and symptomatology of this disorder.

The relevance of reward pathways for schizophrenia.

An increasingly influential perspective conceptualizes both obesity and overeating as a food addiction accompanied by corresponding brain changes. Because there are far-reaching implications for clinical practice and social policy if it becomes widely accepted, a critical evaluation of this model is important. We examine the current evidence for the link between addiction and obesity, identifying several fundamental shortcomings in the model, as well as weaknesses and inconsistencies in the empirical support for it from human neuroscientific research.

Obesity and the brain: how convincing is the addiction model?

Binge eating is associated with obesity and has been conceptualized as "food addiction." However, this view has received only inconsistent support in humans, and limited evidence relates key neurocircuitry to the disorder. Moreover, relatively few studies have used pharmacologic functional magnetic resonance imaging to probe the underlying basis of altered eating behaviors.

Neural and behavioral effects of a novel mu opioid receptor antagonist in binge-eating obese people.

The mu-opioid system has a key role in hedonic and motivational processes critical to substance addiction. However, existing mu-opioid antagonists have had limited success as anti-addiction treatments. GSK1521498 is a selective and potent mu-opioid antagonist being developed for the treatment of overeating and substance addictions. In this study, 28 healthy participants were administered single doses of GSK1521498 20 mg, ethanol 0.5 g/kg body weight, or both in combination, in a double blind placebo controlled four-way crossover design. The primary objective was to determine the risk of significant adverse pharmacodynamic and pharmacokinetic (PK) interactions. The effects of GSK1521498 on hedonic and consummatory responses to alcohol and the attentional processing of alcohol-related stimuli, and their modulation by the OPRM1 A118G polymorphism were also explored. GSK1521498 20 mg was well tolerated alone and in combination with ethanol. There were mild transient effects of GSK1521498 on alertness and mood that were greater when it was combined with ethanol. These effects were not of clinical significance. There were no effects of GSK1521498 on reaction time, hedonic or consummatory responses. These findings provide encouraging safety and PK data to support continued development of GSK1521498 for the treatment of alcohol addiction.

The effects of alcohol on the pharmacokinetics and pharmacodynamics of the selective mu-opioid receptor antagonist GSK1521498 in healthy subjects.

With antiobesity agents, weight loss can emerge from an array of metabolic, cognitive and behavioural changes that translate into weight change over time. In early drug development, characterising these changes can actually be more informative than simply measuring weight loss. Biomarkers for these mechanisms can be used to determine whether potential compounds are worth developing further by providing proof of mechanistic action and detecting early signs of neuropsychiatric adverse effects. In this review, we examine potential biomarkers for effects on metabolism and satiety, hedonics and motivation, and eating behaviour. We also review biomarkers for early detection of neuropsychiatric adverse effects.

Article	Year
The relevance of reward pathways for schizophrenia. Current opinion in psychiatry\| PubMed ID: 20051858	2010
Obesity and the brain: how convincing is the addiction model? Nature reviews. Neuroscience\| PubMed ID: 22414944	2012
Neural and behavioral effects of a novel mu opioid receptor antagonist in binge-eating obese people. Biological psychiatry\| PubMed ID: 23245760	2013
The effects of alcohol on the pharmacokinetics and pharmacodynamics of the selective mu-opioid receptor antagonist GSK1521498 in healthy subjects. Journal of clinical pharmacology\| PubMed ID: 23934621	2013
Central nervous system biomarkers for antiobesity drug development. Drug discovery today\| PubMed ID: 23993917	2013

Hisham Ziauddeen

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