A dose-response study of anorectic drug effects on food intake, self-stimulation, and stimulation-escape

Kornblith, Carol L.; Hoebel, Bartley G.

doi:10.1016/0091-3057(76)90039-3

Cited by 48 publications

(14 citation statements)

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“…Although the latter notion is supported by the observation of significant anorexia to a PP A dosage of 5. mg/kg (Kornblith & Hoebel, 1976), approximate equivalence of dose-response curves for the anorexia induced by PPA and for the taste aversion induced by PPA has also been observed (Wellman & Peters, 1980, Experiment 1). Moreover, the dosedependent suppression of water intake to PP A observed in Experiment 2 demonstrates that the anorectic activity of PP A is nonspecific and indirectly suggests that the anorexia induced by PP A may be a consequence of some aversive action of the drug.…”

Section: Resultsmentioning

confidence: 98%

“…The precise relationship between elicited and natural feeding and drinking, however, remains controversial (Valenstein, 1973), and the influence of PPA on ingestive behavior was examined in animals maintained under ad-lib feeding and drinking schedules. Inasmuch as earlier feeding (Kornblith & Hoebel, 1976;Wellman & Peters, 1980) and conditioned taste aversion (Experiment 1) testing examined the influence of PP A on consummatory behavior displayed by moderately deprived rats, Experiment 2 sought to determine the specificity of the anorectic properties of PP A by an examination of the influence of PPA (10, 20, and 40 mg/ kg) on water intake by 23.5-h water-deprived rats.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

“…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) reported that PPA Portions of this report were presented at the annual meeting of the Southwestern Psychological Association, Houston, 1981. Requests for reprints should be directed to the r11'St author at the Department of Psychology, Texas A&M University, College Station, 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.…”

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confidence: 99%

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

1981

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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...

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Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

“…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) reported that PPA Portions of this report were presented at the annual meeting of the Southwestern Psychological Association, Houston, 1981. Requests for reprints should be directed to the r11'St author at the Department of Psychology, Texas A&M University, College Station, 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.…”

mentioning

confidence: 99%

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

1981

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Evalutation of the pharmacological similarities between phenlpopanolamine andamphetamine: Effects on schedule‐controlled behavior

Wagner

Jarvis²

1990

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In an effort to determine the degree to which the repeated administration of phenylpropanolamine (PPA) results in the development of tolerance to its disruptive effects on operant responding as well as cross-tolerance to the effects of acutely administered amphetamine, water-deprived rats were first trained on a fixed-ratio 5 (FR-5) schedule for water presentation. Dose-response curves for the effects of PPA and amphetamine (administered IP, 15 min presession) were then determined (ED50 = 35.0 and 2.6 mg/kg, respectively) followed by the chronic administration of 40.0 mg/kg PPA (administered IP, 15 min prior to each session). When responding returned to prechronic rates, the dose-response curves were redetermined for both PPA (ED50 = 220 mg/kg) and amphetamine (ED50 = 4.8 mg/kg). In a second set of rats, trained under similar conditions, it was observed that pretreatment with alpha-methyltyrosine (AMT, 100 mg/kg IP, 2 h presession) antagonized the disruptive effects of both PPA and amphetamine, whereas pretreatment with reserpine (0.31 mg/kg, IP, 12 h presession) antagonized the disruptive effects of PPA, but exacerbated the disruptive effects of amphetamine. In a separate experiment, the repeated administration of PPA 100 mg/kg or 200 mg/kg IP resulted in no long-lasting depletions of rat striatal dopamine, serotonin, or 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations. These observations indicate that PPA and amphetamine share a similar mechanism of action to the degree that cross-tolerance develops, but which is nonetheless dissociable with respect to their differential sensitivity to antagonists and their neurotoxic efficacy.

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Brain-Stimulated Reward and Control of Autonomic Function: Are They Related?

Halperin¹,

Pfaff²

1982

The Physiological Mechanisms of Motivation

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A dose-response study of anorectic drug effects on food intake, self-stimulation, and stimulation-escape

Cited by 48 publications

References 16 publications

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

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

Evalutation of the pharmacological similarities between phenlpopanolamine andamphetamine: Effects on schedule‐controlled behavior

Brain-Stimulated Reward and Control of Autonomic Function: Are They Related?

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