PHARMACOLOGICAL CONTROL OF APPETITE: COMPARATIVE STUDY OF FORMAMIDINES AND OTHER AGENTS WHICH INCREASE FEEDING
Abstract
A simple and effective animal model for the screening of appetite stimulants (orexigenic agents) has been described. This model has the advantage over other models in that feed-activity is independent of water consumption and thus may be used to screen agents which may mimic the physiological state of hunger (as opposed to thirst). This model has been verified by a number of different classes of CNS active agents which have been reported to possess feeding activity in other systems and in other species (e.g. clonidine, librium, cyproheptadine, CDC, chlorpromazine, pentobarbital, 2-Deoxy-D-Glucose, theobromine, theophylline, and caffeine). This model has been employed to verify the orexigenic activity of the formamidines, including chlordimeform (CDM). CDM and other formamidines increase 3 hour food intake in non-food deprived (NFD) rats by as much as 5 times control levels, with little or no change in overall 24 hour food intake. The orexigenic activity of the formamidines can be dissociated from their CNS stimulant and local anesthetic-like actions, since neither amphetamine, cocaine, nor holocaine increased 3 hour food intake. Quinine (0.25 and 0.5%) adulterated food intake was depressed to the same degree in both control and CDM treated rats. These results suggest that CDM does not produce feeding as a consequence of increasing taste sensitivity or palatability of food. Pharmacological antagonism studies were carried out to determine the dependence of CDM induced feeding on serotonergic, dopaminergic, or adrenergic systems. Pretreatment with propranolol, phenoxybenzamine, tolazoline, and apomorphine did not alter CDM feeding. Thus, alpha and beta adrenergic systems are not necessary for CDM induced feeding. Pretreatment with haloperidol, quipazine, amphetamine, and fenfluramine did significantly attenuate CDM induced feeding. Thus, the normal integrity of serotonergic and dopaminergic systems are necessary for the expression of CDM induced feeding. CDM has been compared to a large number of structurally and pharmacologically distinct appetite stimulants including clonidine (alpha adrenergic agonist), librium (anxiolytic), cyproheptadine (serotonergic antagonist), theophylline (phosphodiesterase inhibitor), 2-DG (glucose antimetabolite), and others. Although CDM and the other appetite stimulants were unlike 2-DG in terms of their glycemic responses and dose response curves, as well as their ancilliary behavioral profiles, they did increase feeding. In contrast, striking similarities were observed between many of these appetite stimulants with respect to their feeding activity tested under many different conditions. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI
Degree
Ph.D.
Subject Area
Nutrition
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