Functional consequences of fenfluramine neurotoxicity.

Title

Functional consequences of fenfluramine neurotoxicity.

Creator

Schechter M D

Publisher

Pharmacology, biochemistry, and behavior

Date

1990
1990-12

Description

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 manifested by the functionally increased discriminative performance observed.

Subject

Male; Animals; Rats; Discrimination Learning/drug effects; Reinforcement Schedule; Fenfluramine/*toxicity; Nervous System Diseases/*chemically induced/psychology; Dose-Response Relationship; Drug; Inbred Strains; Conditioning; Operant/drug effects

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

623–626

Issue

4

Volume

37

Citation

Schechter M D, “Functional consequences of fenfluramine neurotoxicity.,” NEOMED Bibliography Database, accessed April 19, 2021, https://neomed.omeka.net/items/show/5621.

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