Amphetamine increases glutamate efflux in the rat ventral tegmental area by a mechanism involving glutamate transporters and reactive oxygen species

Marina Wolf, Chang Jiang Xue, Yong Li, David Wavak

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

We have shown that amphetamine produces a delayed and sustained increase in glutamate levels in the ventral tegmental area, a region containing dopamine cell bodies important in acute and chronic effects of amphetamine administration. The present study characterized the mechanism underlying amphetamine-induced glutamate efflux. It was abolished by the glutamate uptake inhibitor dihydrokainate, but unaffected by perfusion with a low Ca2+/high Mg2+ solution, implicating glutamate transporters. Because reactive oxygen species inhibit glutamate uptake, we examined the effect of amphetamine on hydroxyl radical formation by perfusing with D-phenylalanine (5 mM) and monitoring p-tyrosine production. Although no increase in hydroxyl radical formation was detected, D-phenylalanine completely prevented the amphetamine-induced increase in glutamate efflux, as did systemic injection of another trapping agent, α-phenyl-N-tert-butyl nitrone (60 mg/kg). Thus, amphetamine-induced glutamate efflux may involve reactive oxygen species. In other studies, we found that repeated coadministration of α-phenyl-N-tert-butyl nitrone with amphetamine attenuated the development of behavioral sensitization. This supports prior results indicating that the increase in glutamate efflux produced by each amphetamine injection in a chronic regimen is important in triggering drug-induced adaptations in ventral tegmental area dopamine neurons, and that such adaptations may in part represent a response to metabolic and oxidative stress.

Original languageEnglish (US)
Pages (from-to)1634-1644
Number of pages11
JournalJournal of Neurochemistry
Volume75
Issue number4
DOIs
StatePublished - Sep 26 2000
Externally publishedYes

Fingerprint

Amino Acid Transport System X-AG
Ventral Tegmental Area
Amphetamine
Rats
Glutamic Acid
Reactive Oxygen Species
Phenylalanine
Hydroxyl Radical
Dopamine
Physiological Stress
Injections
Oxidative stress
Dopaminergic Neurons
Neurons
Tyrosine
Oxidative Stress
Perfusion
Cells
Monitoring

Keywords

  • α-Phenyl-N-tert-butyl nitrone
  • Amphetamine
  • Glutamate uptake
  • Microdialysis
  • Reactive oxygen species
  • Ventral tegmental area

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Amphetamine increases glutamate efflux in the rat ventral tegmental area by a mechanism involving glutamate transporters and reactive oxygen species. / Wolf, Marina; Xue, Chang Jiang; Li, Yong; Wavak, David.

In: Journal of Neurochemistry, Vol. 75, No. 4, 26.09.2000, p. 1634-1644.

Research output: Contribution to journalArticle

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