Effect of D-amphetamine on the extracellular concentrations of glutamate and dopamine in iprindole-treated rats

J. Frank Nash, Bryan K. Yamamoto

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

A single administration of d-amphetamine and iprindole has been reported to produce selective, long-lasting decreases in brain dopamine (DA) content because of axon terminal degeneration. It has been found that the noncompetitive glutamate (GLU) antagonist, MK 801, blocks d-amphetamine-induced DA depletion in iprindole-treated rats. In the present study, the effect of d-amphetamine (9.2 mg/kg) and iprindole (10 mg/kg) on the extracellular concentrations of DA and GLU was determined in the striatum of awake, freely moving rats by the use of in vivo microdialysis. D-Amphetamine significantly increased DA and GLU efflux in the striatum of iprindole-treated rats as compared to the vehicle-treated group. The increase in the extracellular concentration of GLU occurred 4-6 hr following drug administration. The concentration of DA was decreased significantly in the striatum of d-amphetamine and iprindole-treated rats 7 days following administration as compared to the vehicle-treated group. Inhibition of tyrosine hydroxylase after α-methylparatyrosine (150 mg/kg) administration attenuated d-amphetamine-induced DA and GLU release. The DA antagonist, haloperidol (1 mg/kg), blocked D-amphetamine-induced GLU release without affecting the increase in the extracellular concentration of DA produced by the combination of D-amphetamine and iprindole. Both α-methylparatyrosine and haloperidol blocked the depletion of DA in the striatum 7 days after d-amphetamine and iprindole as compared to the vehicle group. In addition, administration of MK-801 (2 mg/kg) 2 hr after d-amphetamine significantly attenuated the long-term (7 day) decrease in striatal DA content produced by the combination of d-amphetamine and iprindole. These data provide direct evidence that amphetamine increases the extracellular concentration of GLU in iprindole-treated rats. Moreover, these data are suggestive that the acute increase in GLU efflux contributes to the long-term damage to DA axon terminals produced by high dose amphetamine administration.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalBrain research
Volume627
Issue number1
DOIs
StatePublished - Nov 5 1993
Externally publishedYes

Keywords

  • Dopamine
  • Glutamate
  • In vivo microdialysis
  • Iprindole
  • Neurotoxicity
  • d-amphetamine

ASJC Scopus subject areas

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

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