On the mechanism of d-amphetamine-induced changes in glutamate, ascorbic acid and uric acid release in the striatum of freely moving rats

Br J Pharmacol. 2000 Feb;129(3):582-8. doi: 10.1038/sj.bjp.0703066.

Abstract

1. The effects of systemic, intrastriatal or intranigral administration of d-amphetamine on glutamate, aspartate, ascorbic acid (AA), uric acid, dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in dialysates from the striatum of freely-moving rats were evaluated using microdialysis. 2. d-Amphetamine (2 mg kg-1) given subcutaneously (s.c.) increased DA, AA and uric acid and decreased DOPAC + HVA, glutamate and aspartate dialysate concentrations over a 3 h period after d-amphetamine. 5-HIAA concentrations were unaffected. Individual changes in glutamate and AA dialysate concentrations were negatively correlated. 3. d-Amphetamine (0.2 mM), given intrastriatally, increased DA and decreased DOPAC + HVA and aspartate dialysate concentrations, but failed to change those of glutamate, AA uric acid or 5-HIAA, over a 2 h period after d-amphetamine. Haloperidol (0.1 mM), given intrastriatally, increased aspartate concentrations without affecting those of glutamate or AA. 4. d-Amphetamine (0.2 mM), given intranigrally, increased AA and uric acid dialysate concentrations and decreased those of glutamate, aspartate and DA; DOPAC + HVA and 5-HIAA concentrations were unaffected. 5. These results suggest that d-amphetamine-induced increases in AA and uric acid and decreases in glutamate concentrations are triggered at nigral sites. The changes in aspartate levels may be evoked by at least two mechanisms: striatal (mediated by inhibitory dopaminergic receptors) and nigral (activation of amino acid carrier-mediated uptake).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Ascorbic Acid / metabolism*
  • Dextroamphetamine / administration & dosage
  • Dextroamphetamine / pharmacology*
  • Dopamine / metabolism
  • Dopamine Antagonists / pharmacology
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dopamine Uptake Inhibitors / pharmacology*
  • Glutamic Acid / metabolism*
  • Haloperidol / pharmacology
  • In Vitro Techniques
  • Injections
  • Male
  • Microdialysis
  • Motor Activity / drug effects
  • Neostriatum / drug effects
  • Neostriatum / metabolism*
  • Oxidation-Reduction
  • Rats
  • Rats, Wistar
  • Stereotaxic Techniques
  • Stereotyped Behavior / drug effects
  • Uric Acid / metabolism*

Substances

  • Dopamine Antagonists
  • Dopamine Uptake Inhibitors
  • 3,4-Dihydroxyphenylacetic Acid
  • Uric Acid
  • Glutamic Acid
  • Haloperidol
  • Ascorbic Acid
  • Dextroamphetamine
  • Dopamine