ANORECTIC DRUGS--ABUSE & BEHAVIORAL MECHANISMS OF ACTION

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There is increasing concern about the use and misuse of anorectic drugs, with more and more prescribed as adjuncts in weight control therapy. The present proposal will investigate the effects of these drugs on patterns of food intake in baboons maintained under minimal deprivation conditions. Food will be continuously available under an operant schedule that differentiates patterning of meals from pattern of pellet intake within meals. Schedule parameters will be chosen so that each animal will have control over initiation as well as termination of feeding throughout the day. Baseline patterns of food intake will be determined by measuring meal frequency, size, duration, and distribution of intake within each meal over several months. The effects of four manipulations on feeding will be assessed in order to compare those effects with later drug effects. Caloric prefeeding, acute deprivation cholecystokinin administration and the availability of an alternate energy source will all be parametrically manipulated. Complete dose-response functions for six amphetamine-like/stimulant anorectic drugs, three fenfluramine-like/sedative anorectic drugs and phenylpropanolamine will be determined. In addition, diazepam, known to increase food intake, and phencyclidine, which should decrease food intake by causing motor deficits, will also be tested. Profiles of the behavioral mechanisms of all these drugs when given on a single dose basis will be developed. Furthermore, the work will analyze the effects of long-term administration of low doses of d-amphetamine and fenfluramine on food intake; cross-tolerance to each other, phenylpropanolamine, and phencyclidine will be examined. The data collected in these studies will enhance the abuse liability data base of the anorectics and, in addition, provide important information about their behavioral mechanisms. This research will add to the large experimental data base on the self-administration of these compounds in primates, and provide important information for the analysis of the behavioral mechanisms of these drugs, e.g., effects on meal size and patterning. Such information will be useful both in evaluation of therapeutic efficacy and in understanding the basic processes involved in eating behavior.