The amine-depleting effects of 5,7-dihydroxytryptamine (5,7-DHT) in C57BL/6 mice do not increase with age

Kevin T. Finnegan, Louis E. DeLanney, Ian Irwin, George A. Ricaurte, J. William Langston

Research output: Contribution to journalArticle

Abstract

A recent approach to identifying the factors that predispose neurons to an early death in Parkinson's or Alzheimer's disease has been study how the effects of specific neurotoxins are altered by increasing maturity. We determined the dose-related serotonin and norepinephrine-depleting effects of the selective neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), in C57BL/6 mice of 2 different ages. Norepinephrine and serotonin in the hippocampus were assayed 1 week after the intracerebroventricular (i.c.v.) administration of 5,7-DHT. 5,7-DHT produced equivalent, dose-related depletion of hippocampal norepinephrine in both age groups. Since the effects of 5,7-DHT on noradrenergic neurons may, at leastin part, depend on the monoamine oxidase (MAO)-generated formation of hydrogen peroxide and associated oxy-radicals,this result suggests that noradrenergic neurons do not become more vulnerable to oxidative stress with aging. We also found that the noradrenergic-depleting effects of 5,7-DHT were blocked by the non-selective MAO inhibitor pargyline (50mg/kg, i.p.), whilethe selective MAO B inhibitor deprenyl (10 mg/kg, i.p.) failed to prevent this depletion. These latter results suggest that it is the A form of MAO that plays an important role in the mechanism of 5,7-DHT-induced noradrenergic toxicy. Somewhat unexpectedly, older mice were found to be less susceptible to the serotonin-depleting effects of 5,7-DHT. Although the mechanism by whichthis compound damages serotonergic neurons is uncertain, our results show that the increased susceptibility of serotonergic neurons to 5,7-DHT in young animals extends well beyond the neonatal period.

Original languageEnglish (US)
Pages (from-to)251-256
Number of pages6
JournalBrain research
Volume496
Issue number1-2
DOIs
StatePublished - Sep 4 1989

Keywords

  • 5,7-Dihydroxytryptamine
  • Aging
  • Monoamine oxidase
  • Neurotoxin
  • Norepinephrine
  • Parkinson's disease
  • Serotonin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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