Concurrent locomotor stimulation and decrease in dopamine release in rats and mice after treatment with the competitive NMDA receptor antagonists D-CPPene and CGS 19755

被引:26
作者
Waters, N
Lundgren, C
Hansson, LO
Carlsson, ML
机构
[1] Department of Physiology and Pharmacology, Division of Pharmacology, S-413 90 Göteborg
关键词
competitive NMDA antagonists; glutamate; dopamine; release; psychosis;
D O I
10.1007/BF01292621
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The present study was aimed al investigating the effects of the competitive N-methyl-D-aspartate (NMDA) receptor antagonists D-CPPene (3-(2-carboxypiperazine-4-yl)-propenyl-1-phosphonic acid) and CGS 19755 (cis-4-(phosphonomethyl)piperidine-2-carboxylic acid) on dopamine (DA) transmission and motor activity in mice and rats. As measures of DA release we used mouse brain 3-methoxytyramine (3-MT) levels, an indirect estimate of DA release, and striatal dialysate measures of DA in conscious and freely moving rats by means of microdialysis. To obtain additional information about monoaminergic neurotransmission, brain tissue levels of DA, DOPAC, HVA, 5-HT and 5-HIAA were measured in both mice and rats. The animals were sacrificed at the time when NMDA antagonist-induced locomotor stimulation was maximal. In mice, D-CPPene and CGS 19755 decreased striatal 3-MT levels, whereas, in general, 3-MT levels in the limbic forebrain were not significantly altered. Treatment with CGS 19755 decreased rat striatal dialysate levels of DA but increased S-HIAA at time points when locomotor activity was increased. D-CPPene and CGS 19755 have been observed to produce psychotic symptoms in man. The present study suggests that these symptoms are not a result of an increase in central dopamine release.
引用
收藏
页码:117 / 129
页数:13
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