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

被引:31
|
作者
Morford, LL
Inman-Wood, SL
Gudelsky, GA
Williams, MT
Vorhees, CV [1 ]
机构
[1] Childrens Hosp Res Fdn, Div Dev Biol, Cincinnati, OH 45229 USA
[2] Univ Cincinnati, Coll Med, Cincinnati, OH 45229 USA
[3] Univ Cincinnati, Coll Pharm, Cincinnati, OH 45267 USA
[4] Childrens Hosp Res Fdn, Pharmacol Res Ctr, Cincinnati, OH 45229 USA
关键词
5-HT; amphetamines; Cincinnati maze; fenfluramine; Morris water maze; reference memory; serotonin;
D O I
10.1046/j.1460-9568.2002.02100.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:491 / 500
页数:10
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