Hypothalamic dopamine and serotonin in the regulation of food intake.

ABSTRACT

Because daily food intake is the product of the size of a meal and the frequency of meals ingested, the characteristic of meal size to meal number during 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 (constituting a change in feeding patterns) as opposed to an understanding of only food intake provides a more insightful dynamic picture reflecting integrated behavior. We have correlated this to simultaneous changes in dopamine and serotonin concentrations and to their postsynaptic receptors, focusing simultaneously on two discrete hypothalamic food-intake-related nuclei, in response to the ingestion of food. The relation between concentrations of dopamine 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 measured in our experiments are discussed. Based on these data, conceptual models are proposed concerning 1) an "afferent-efferent neurotransmitter unit," with facilitatory or inhibitory neuropeptide properties to generate an appropriate neuroendocrine and neuronal response that ultimately modifies food intake; 2) initiation and termination of a meal, thereby determining the number and size of a meal under normal conditions; and 3) a schema integrating 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 on simultaneous changes in dopamine and serotonin concentrations in the LHA and VMN with the onset of acute anorexia of nicotine infusion and acute hyperphagia of nicotine cessation. Data concerning the role of sex-related hormones on dopamine and serotonin with regard to the LHA and VMN in relation to the modulation of food intake are also presented.