Impaired spatial and sequential learning in rats treated neonatally with d-fenfluramine

d‐Fenfluramine, a serotonin releaser, was administered to neonatal rats on postnatal days 11–20 (a stage of hippocampal development analogous to third trimester human ontogeny). As adults, the d‐fenfluramine‐treated offspring exhibited dose‐related impairments of sequential and spatial learning and...

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Bibliographic Details
Published in:The European journal of neuroscience 2002-08, Vol.16 (3), p.491-500
Main Authors: Morford, L. L., Inman-Wood, S. L., Gudelsky, G. A., Williams, M. T., Vorhees, C. V.
Format: Article
Language:English
Subjects:
5-HT
amphetamines
Animals
Animals, Newborn
Behavior, Animal - drug effects
Behavior, Animal - physiology
Body Weight - drug effects
Body Weight - physiology
Cincinnati maze
Dose-Response Relationship, Drug
Female
fenfluramine
Fenfluramine - adverse effects
Hippocampus - drug effects
Hippocampus - growth & development
Hippocampus - metabolism
Humans
Learning - drug effects
Learning - physiology
Male
Maze Learning - drug effects
Maze Learning - physiology
Memory Disorders - chemically induced
Memory Disorders - metabolism
Memory Disorders - physiopathology
Morris water maze
Pregnancy
Prenatal Exposure Delayed Effects
Psychomotor Performance - drug effects
Psychomotor Performance - physiology
Rats
Rats, Sprague-Dawley
reference memory
serotonin
Serotonin - metabolism
Serotonin Uptake Inhibitors - pharmacology
Survival Rate
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Summary:d‐Fenfluramine, a serotonin releaser, was administered to neonatal rats on postnatal days 11–20 (a stage of hippocampal development analogous to third trimester human ontogeny). As adults, the d‐fenfluramine‐treated offspring exhibited dose‐related impairments of sequential and spatial learning and reference memory in the absence of sensorimotor impairments. Procedures to minimize stress and to control for other performance effects prior to testing for spatial learning demonstrated that nonspecific factors did not account for the selective effects of d‐fenfluramine on learning and memory. Developmental d‐fenfluramine‐induced spatial and sequential learning deficits are similar to previous findings with developmental MDMA treatment. By contrast, recent findings with developmental d‐methamphetamine treatment showed spatial learning deficits while sparing sequential learning. The spatial learning effects common to all three drugs suggest that they may share a common mechanism of action, however, the effects are not related to long‐lasting changes in hippocampal 5‐HT levels as no differences were found in adulthood. Whether the cognitive deficits are related to the effects of substituted amphetamines on corticosteroids, other aspects of the 5‐HT system, or some unidentified neuronal substrates is not known, but the data demonstrate that these drugs are all capable of inducing long‐term adverse effects on learning.
ISSN:0953-816X
1460-9568
DOI:10.1046/j.1460-9568.2002.02100.x