Functional consequences of fenfluramine neurotoxicity

Pharmacology, Biochemistry, and Behavior
M D Schechter

Abstract

Male Sprague-Dawley rats were trained to discriminate the anorectic drug d,l-fenfluramine (2.0 mg/kg intraperitoneally administered) from its vehicle using a food-motivated (fixed-ratio 10 schedule) two-lever operant task. Once trained, doses of 0.5, 1.0 and 1.5 mg/kg fenfluramine tested 20 min after IP administration produced dose-responsive discrimination performance. Subsequently, noncontingent twice-a-day administrations of 1 ml/kg saline were made for 4 days and the dose-effect relationship redetermined on the 13th to 15th day after initiation of the chronic saline regimen. Results of these dose-response experiments indicated that there was no significant effect upon fenfluramine discrimination after multiple saline injections or after 10 days without training. Following four days of retraining, 6.25 mg/kg fenfluramine twice-a-day for four days was followed 10 days later by another dose-response determination. This purportedly neurotoxic regimen of fenfluramine significantly increased the rats' ability to discriminate fenfluramine. These results suggest the possibility that chronic release of serotonin or selective damage to serotonin-containing neurons produced by fenfluramine may lead to postsynaptic supersensitivity as ...Continue Reading

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Citations

Mar 1, 1991·Pharmacology, Biochemistry, and Behavior·M D Schechter
Jan 1, 1996·Pharmacology, Biochemistry, and Behavior·D Marona-LewickaD E Nichols
Feb 1, 1996·Pharmacology, Biochemistry, and Behavior·L E Baker, M M Makhay
May 1, 1994·Progress in Neuro-psychopharmacology & Biological Psychiatry·S M Meehan, M D Schechter
Jul 21, 1998·Annals of the New York Academy of Sciences·M H BaumannR B Rothman
May 1, 1998·Annals of the New York Academy of Sciences·Michael H BaumannRichard B Rothman

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