d-Fenfluramine anorexia : Dissociation of ingestion rate, meal duration, and meal size effects

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 1997-05, Vol.57 (1-2), p.223-229
• Main Authors: KAPLAN, J. M, DONAHEY, J, BAIRD, J.-P, SIMANSKY, K. J, GRILL, H. J
• Format: Article
• Language: English
• Subjects: Animals; Anorexia - chemically induced; Appetite Depressants - adverse effects; Biological and medical sciences; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Feeding Behavior - drug effects; Fenfluramine - adverse effects; General and cellular metabolism. Vitamins; Habituation, Psychophysiologic; Male; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Serotonin Uptake Inhibitors - adverse effects; Stereoisomerism; Time Factors
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/S0091-3057(96)00340-1

In the present study, we ask whether the suppressive effect of d-fenfluramine (d-FEN) on short-term intake can be better explained in terms of a primary action on particular behavioral parameters (e.g., ingestion rate or meal duration), as proposed by several investigators, or in terms of a primary effect on an intake "target" that can be achieved via diverse behavioral strategies. We applied two specialized intake testing paradigms that constrain the behavioral structure of the rat's meal in different ways, and determined whether or not the meal-size result varied in turn. (1) In the intraoral intake test, the rate of ingestion was clamped by the rate (1.0 ml/min) at which the test stimulus (12.5% glucose) was intraorally delivered. A d-FEN (3 mg/kg) suppression of intraoral intake was obtained demonstrating that ingestion rate adjustment is not necessary for the anorexic effect. In addition, for both d-FEN and vehicle conditions, comparable amounts were consumed when the intraoral intake test was either continuous or interrupted for 10 min beginning 6 min after test onset. For d-FEN, the increase in meal duration (mean = 11.98 min) required to compensate for the imposed interruption indicates that the drug does not specify an absolute limit for meal duration. (2) In the drop size-controlled spout-licking test, the volume of 12.5% glucose delivered for each lick was fixed at either 8 or 4 microliters. There was an overall reduction in intake with d-FEN (0.75 mg/kg), but as under vehicle injection conditions, the number of licks emitted approximately doubled when lick volume was halved. As a result, meal size was unaffected by the drop size manipulation. The drop size manipulation affected several other behavioral parameters under respective d-FEN and vehicle injection conditions, including: average rate of ingestion (ml/min), initial ingestion rate, and ingestion duration (meal duration minus pause time). The two experiments together demonstrate that the anorexic effect of d-FEN does not depend on adjustment of any particular behavioral parameter. The results suggest, rather, that given doses of d-FEN establish a particular degree of intake suppression that the rat defends via diverse behavioral strategies.