alpha-Methyl-p-tyrosine pretreatment partially prevents methamphetamine-induced endogenous neurotoxin formation

Brain Res. 1990 May 7;515(1-2):269-76. doi: 10.1016/0006-8993(90)90606-c.

Abstract

Depletion of brain dopamine (DA) by pretreatment with the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMT) has been shown to prevent the long-term neurotoxic effects of methamphetamine (MA). In addition, it has recently been reported that the neurotoxins 6-hydroxydopamine (6-OHDA) and 5,6-dihydroxytryptamine (5,6-DHT) are formed endogenously in neostriatum and hippocampus, respectively, following a single neurotoxic dose of MA. We, therefore, have examined the ability of AMT pretreatment to prevent the MA-induced formation of 6-OHDA and 5,6-DHT. We report that AMT pretreatment significantly decreases the frequency with which 6-OHDA and 5,6-DHT are detected following MA administration. Neurotoxin formation is compared with brain levels of DA and 5-hydroxytryptamine (5-HT) 2 weeks after MA administration. It is concluded that the ability of AMT to attenuate both 6-OHDA formation and long-term depletions of DA is due to a decrease in the MA-releasable pool of DA. The effect of AMT on MA-induced depletions of 5-HT is less clear and may involve additional factors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5,6-Dihydroxytryptamine / metabolism*
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Dopamine / metabolism*
  • Hydroxydopamines / metabolism*
  • Male
  • Methamphetamine / pharmacology*
  • Methyltyrosines / pharmacology*
  • Neurotoxins / metabolism*
  • Neurotoxins / pharmacology
  • Oxidopamine
  • Rats
  • Rats, Inbred Strains
  • alpha-Methyltyrosine

Substances

  • Hydroxydopamines
  • Methyltyrosines
  • Neurotoxins
  • Methamphetamine
  • alpha-Methyltyrosine
  • Oxidopamine
  • Dopamine
  • 5,6-Dihydroxytryptamine