The neurotoxic effects of p-chloroamphetamine in rat brain are blocked by prior depletion of serotonin.
Brain Res
; 578(1-2): 177-85, 1992 Apr 24.
Article
em En
| MEDLINE
| ID: mdl-1511276
ABSTRACT
Systemic administration of p-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 of p-chlorophenylalanine and reserpine. The results show 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
P-Cloroanfetamina
/
Reserpina
/
Encéfalo
/
Serotonina
/
Neurotoxinas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
1992
Tipo de documento:
Article