Age-associated changes in the dopamine synthesis as determined by GTP cyclohydrolase I inhibitor in the brain of senescence-accelerated mouse-prone inbred strains (SAMP8)

Neurosci Res. 1999 Oct;35(1):31-6. doi: 10.1016/s0168-0102(99)00063-2.

Abstract

Our objective in this study was to elucidate the mechanism underlying the decrease in dopamine (DA) levels in the brain with ageing We administered 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of GTP cyclohydrolase I to senescence-accelerated mouse-prones (SAMP8), to inhibit DA and serotonin syntheses, and following immunohistochemical staining, analyzed the immunoreactive intensities (IR-Is) for DA in the nigrostriatal dopaminergic neurons by microphotometry. The DA-IR-Is in the substantia nigra pars compacta and neostriatum of young mice (2 months old) reached a minimal value 3 h after DAHP administration and returned to the control value 12 h after the administration. However, in aged mice (10 months old), the minimal value was reached 6 h after the administration and the value remained at approximately 70 and 80% of the control value at 24 and 72 h, respectively, after DAHP administration. The results suggest that DA turnover is lower in aged mice than in young mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Dopamine / biosynthesis*
  • Enzyme Inhibitors / pharmacology
  • Female
  • GTP Cyclohydrolase / antagonists & inhibitors*
  • Hypoxanthines / pharmacology*
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred Strains
  • Neostriatum / drug effects
  • Neostriatum / growth & development
  • Neostriatum / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Serotonin / biosynthesis
  • Substantia Nigra / drug effects
  • Substantia Nigra / growth & development
  • Substantia Nigra / metabolism*

Substances

  • Enzyme Inhibitors
  • Hypoxanthines
  • Serotonin
  • GTP Cyclohydrolase
  • 2,4-diaminohypoxanthine
  • Dopamine