Bidirectional control of palatable food consumption through a common benzodiazepine receptor: theory and evidence

A classical approach to the control of food consumption has been to assume separate mechanisms for the arousal to eat, on the one hand, and the satiation of feeding responses, on the other. The present paper is concerned with a single, and a comparatively simple, neuronal mechanism which is endowed with properties to allow the complete determination of the level of feeding, from hyperphagia to anorexia. The model for the control of feeding, which is presented here, draws attention to the benzodiazepine receptor found distributed through the brain, and present in certain hypothalamic nuclei. Recent evidence which characterizes the receptor is reviewed, and the various categories of benzodiazepine receptor ligands are described. Pharmacological data, collected in a palatable food consumption model using non-food-deprived rats, demonstrate that benzodiazepine receptor agonists produce hyperphagia, benzodiazepine receptor inverse agonists produce anorexia, and benzodiazepine receptor antagonists block both effects. Hence, bidirectional control of food intake can be achieved through differential ligand action at a common set of receptors. Speculatively, these data can be extended, if it is assumed that two endogenous ligands exist in the brain which act like benzodiazepine agonist and inverse agonist, respectively. Evidence for the presence in hypothalamic nuclei of endogenous ligands of the latter kind is discussed. Benzodiazepine withdrawal-induced anorexia is also described, and is taken as evidence for the part played by feeding mechanisms in the development of benzodiazepine physical dependence.