Pharmacokinetics of systemically administered tyrosine: A comparison of serum, brain tissue and in vivo microdialysate levels in the rat

Rodolfo Bongiovanni, Bryan K. Yamamoto, Catherine Simpson, George E. Jaskiw

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Tyrosine uptake has been reported to differ across brain regions. However, such studies have typically been conducted over brief intervals and in anesthetized rats; anesthesia itself affects amino acid transport across the blood-brain barrier. To address these concerns, serum, brain tissue and in vivo microdialysate tyrosine levels were compared for 0-3 h after administration of tyrosine [0.138-1.10 mmol/kg intraperitoneally (i.p.)] to groups of awake rats. Serum and brain tissue tyrosine levels increased linearly with respect to dose. Basal tissue tyrosine levels varied significantly across brain regions [medial prefrontal cortex (MPFC), striatum, hypothalamus, and cerebellum], but the rate of tyrosine uptake was similar for hypothalamus, striatum and MPFC. For brain regions in which tyrosine levels in both microdialysate and tissue were assayed, namely MPFC and striatum, there was a high degree of correlation between tyrosine levels in tissue and in microdialysate. Increasing brain tyrosine levels had no effect on DA levels in MPFC microdialysate. We conclude that (i) regional differences in the response of dopamine neurons to systemic tyrosine administration cannot be attributed to pharmacokinetic factors; (ii) in vivo microdialysate provides an excellent index over time and across a wide range of tyrosine doses, of brain tissue tyrosine levels; and (iii) increases in brain tyrosine levels do not affect basal DA release in the MPFC.

Original languageEnglish (US)
Pages (from-to)310-317
Number of pages8
JournalJournal of Neurochemistry
Volume87
Issue number2
DOIs
StatePublished - Oct 1 2003
Externally publishedYes

Keywords

  • Amino acids
  • Large neutral amino acids
  • Medial prefrontal cortex
  • Microdialysis
  • Striatum
  • Tyrosine

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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