BBSRC psychopharmacology of appetite studentship proposal

Obesity is a condition of abnormal or excessive fat accumulation caused by an excess of energy intake over energy expenditure. Obesity increases the risk of developing type II diabetes, coronary heart disease, hypertension and some cancers. It is estimated that over 250 million people suffer from obesity worldwide. The UK has one of the highest rates of obesity in Europe, with 20% of the population defined as obese and over 50% overweight. The development of safe and effective therapeutics is therefore imperative. An effective means to help weight loss, as part of a comprehensive programme, is to prescribe drug treatments designed to reduce appetite and food consumption, without significant side effects. At present, drug treatment for obesity is limited to three products that have entered the market. Orlistat is a lipase inhibitor that works by preventing the breakdown and absorption of fat in the intestinal system. However, its use is limited by gastrointestinal side effects. Sibutramine is a serotonin-noradrenaline reuptake inhibitor that influences brain mechanisms of satiety; however, the drug also affects the cardiovascular system, which limits its utility. Rimonabant is a cannabinoid CB1 receptor antagonist that acts on brain mechanisms of satiety and reward and which is marketed in the UK and more than 40 other countries. However, the drug has not been approved for sale in the US due to concern about increased risk of depression and suicide. Therefore, there is a need for improved therapies for obesity. Similarly, a demand exists for human experimental models to enable novel drug therapies to be screened rapidly for efficacy. Furthermore, there is a need for increased understanding of the psychopharmacology of appetite in humans so that drug-induced changes in neurochemical systems in the brain can be linked to specific changes in eating behaviour and hence the effectiveness of future therapies improved. We will use a customized programme (Universal Eating Monitor (UEM) model) to characterize the effects of appetite altering drugs on eating behaviour in healthy volunteers. The UEM model has recently been validated with the appetite-suppressant sibutramine (Halford et al. 2008). The proposed project will involve recruitment of healthy volunteers to studies in which within-meal variables will be assessed using the UEM model. We will compare the effects of satiety manipulations (e.g. preloading) and palatability manipulations (e.g. enhancing taste quality) with the effects of administration of available appetite altering drugs (with proven safety). Studies will be double-blind and placebo-controlled. Data collected will be analysed to determine the effects of the manipulations on total food intake in the test meal, rate of consumption throughout the meal, duration of eating, and ratings of palatability, hunger and fullness. These data will allow a comprehensive characterization of the effects of appetite altering drugs on eating and hence have implications for understanding of the neurochemistry of appetite control and the development of more effective therapies for eating disorders. The project will also provide further validation of the UEM system as a robust, objective measure of anti-obesity treatment interventions. The student will benefit from training in project management, research ethics, experimental design, volunteer recruitment and complex data handling and analysis and will gain extensive knowledge of neuropharmacological and psychological controls of eating. The project will provide advanced skills in both experimental psychological and psychopharmacological methods as applied to the study of human eating behaviour, which is one of the most active areas of drug research and development in the pharmaceutical industry. This rare combination of expertise in the UK will make the student very well qualified for future positions within research and development in either academia or industry.