Hypothalamic dopamine and serotonin in the regulation of food intake

Because daily food intake is the product of the size of a meal and the freq uency of meals ingested, the characteristic of meal size to meal number dur ing a 24-h light-dark cycle constitutes an identifiable pattern specific to normal states and obesity and that occurs during early cancer anorexia. An understanding of simultaneous changes in meal size and meal number (consti tuting a change in feeding patterns) as opposed to an understanding of only food intake provides a more insightful dynamic:picture reflecting integrat ed behavior. We have correlated this to simultaneous changes in dopamine an d serotonin concentrations and to their postsynaptic receptors, focusing si multaneously on two discrete hypothalamic food-intake-related nuclei, in re sponse to the ingestion of food, The relation between concentrations of dop amine and serotonin limited to the lateral hypothalamic area (LHA) and the ventromedial nucleus (VMN) as they relate to the influence of meal size and meal number during the hyperphagia of obesity and anorexia of cancer as me asured in our experiments are discussed. Based on these data, conceptual mo dels are proposed concerning: 1) an "afferent-efferent neurotransmitter uni t," with facilitatory or inhibitory neuropeptide properties to generate an appropriate neuroendocrine and neuronal response that ultimately modifies f ood intake; 2) initiation and termination of a meal,; thereby determining t he; number and size of a meal under normal conditions; and 3) a schema inte grating the onset mechanism of cancer anorexia. Nicotine is used as a tool to further explore the relation of meal size to meal number, with a focus o n simultaneous changes in dopamine and serotonin concentrations in the LHA and VMN with the onset of acute anorexia of nicotine infusion and acute hyp erphagia of nicotine cessation. Data concerning the role of sex-related hor mones on dopamine and serotonin with regard to the LHA and VMN in relation to the modulation of food intake are also presented. Nutrition 2000;16:843- 857. (C) Elsevier Science Inc. 2000.