Conditioned taste aversion and unconditioned suppression of water intake induced by phenylpropanolamine in rats

Abstract

The putative aversive properties of phenylpropanolamine WPA), an analog of amphetamine, were delineated in two behavioral tests. In a conditioned taste aversion paradigm, PPA (10, 20, or 40 mg/kg) was found to induce dose-dependent taste aversion, whereas identical dosages of PPA were found to produce dose-dependent unconditioned suppression of water intake in 23.5-h water-deprived rats. Comparison of the dose-response curves for the aversion and hypodipsia induced by PPA indicates that a single process, presumably malaise or toxicosis, may mediate these effects. These findings question the notion that PPA induces anorexia via activation of a CNS satiety mechanism and lend credence to the suggestion advanced herein that nonspecific malaise may mediate the moderate anorectic activity of PPA observed in rodents and humans.Of the numerous drugs ascribed anorectic properties over the past four decades (Aviado, 1970; Costa & Garratini, 1970), phenylpropanolamine (PPA) has perhaps held the greatest promise as a weight control substance for obese humans. Phenylpropanolamine, an analog of amphetamine, was reported to induce moderate anorexia and weight loss in rodents and humans but was without the properties of arousal and dependence that are characteristic of the amphetamines (Aviado, 1970;Epstein, 1959;Griboff, Berman, & Silverman, 1975;Kornblith & Hoebel, 1976). It is precisely because of these properties (and lack thereof) that over-the-counter weight loss preparations containing PP A have enjoyed considerable commercial success.Although PP A is known to induce anorexia, the precise mechanism of this effect is unclear. A major problem in the interpretation of the anorexia induced by drugs such as PP A derives from the notion that all or a portion of the anorexia may result not from the induction of satiety, but rather from some malaiseinducing effect such as hyperthermia, gastrointestinal irritation, or arousal (Carey, 1979;Carlton, 1963;Wellman & Peters, 1980). With regard to the possible side effects of PP A, Epstein (1959) and Kornblith and Hoebel (1976) treatment did not induce overt psychomotor arousal, whereas Wellman (unpublished findings) found that a moderate (20 mg/kg) PP A dosage did not induce hyperthermia in rats. These data tentatively suggest that PP A-induced anorexia is not the result of malaise, yet several tests remain to be completed. Hoebel, Hernandez, and Thompson (1975) noted that a treatment dosage of 40 mg/kg PP A induced discomfort and general debilitation, but they did not determine whether any dosage of PP A will induce conditioned taste aversion. Experiment 1 therefore provides a dose-response examination of the putative aversive properties of PP A (10, 20, and 40 mg/kg) as indexed by a conditioned taste aversion paradigm. EXPERIMENT 1 MethodAnimals. The animals were 40 male Sprague-Dawley albino rats weighing 325-440 g at the beginning of the experiment. The rats were housed individually in standard wire-mesh cages in a temperature-controlled (23°-25°C) colony under a standard light...