The neurotoxic effects of p-chloroamphetamine in rat brain are blocked by prior depletion of serotonin.
The neurotoxic effects of p-chloroamphetamine in rat brain are blocked by prior depletion of serotonin.
复制标题
对氯苯丙胺对大鼠大脑的神经毒性作用可以通过预先消耗血清素来阻断。
DOI：
10.1016/0006-8993(92)90246-6
复制
发表时间：
1992
期刊：
影响因子：
2.9
通讯作者：
Molliver,ME
中科院分区：
文献类型：
--
作者：
Berger,UV;Grzanna,R;Molliver,ME
Systemic administration ofp-chloroamphetamine(PCA) causes degeneration of serotonergic (5-HT) axons, but recent data indicate that this drug itself is not neurotoxic when applied directly to 5-HT axons. The present study was designed to test whether the toxic effects of PCA in the brain are dependent on release of endogenous 5-HT and to identify which stores of 5-HT are involved. The long-term effects of PCA on brain levels of 5-HT and on central 5-HT axons were determined in rats that had been initially depleted of 5-HT by administration ofp-chlorophenylalanineand reserpine. The resultsshow that transient depletion of 5-HT provides substantial protection against subsequent PCA-induced degeneration of 5-HT axon terminals; the neurotoxicity induced by PCA thus appears to be dependent on the presence of endogenous stores of 5-HT. In addition, the protective effect of 5-HT depletion is found only after pretreatment regimens that deplete peripheral as well as central stores of 5-HT. We interpret this finding as evidence that release of 5-HT from peripheral storage sites may be necessary for the expression of PCA-induced toxicity. Based on these results, we propose that central neurotoxicity is not induced by a direct action of PCA alone but may require or be augmented by a toxic metabolite of 5-HT.
