Benzodiazepines and appetite: Recent pre-clinical advances and their clinical implications

Since their introduction in the early 1960s it has been known that benzodiazepines potently increase food intake in many animal species, including higher primates. Behavioural and pharmacological evidence shows that this hyperphagic effect of benzodiazepines is not secondary to their anxiolytic properties, and can also be dissociated from sedative and muscle-relaxant effects. The hyperphagic response appears to be due to a direct effect on appetite mechanisms, and certainly arises from interactions of drugs with specific benzodiazepines recognition sites in the brain. The discovery of so-called ‘inverse agonists’, which bind to benzodiazepine sites, has led to experiments which show that they reduce food consumption and can block benzodiazepine-induced hyperphagia. The most recent research in this area shows that benzodiazepines enhance the hedonic quality of taste stimuli, and indicates that this may determine their effects on food preferences and food consumption. This evidence is reviewed in this article. Attention is also drawn to recent experimental work in patients with eating disorders; anorexia nervosa and bulimia. Both groups show heightened taste responsiveness to sweet, palatable taste. Further study of benzodiazepine effects on appetite should throw new light on neurochemical determinants of taste palatability. Inverse agonists acting at benzodiazepine receptors may provide examples of drugs which could be used to attenuate taste responsiveness to highly palatable foods.