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)

Our objective in this study was to elucidate the mechanism underlying the d ecrease 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 immuno reactive intensities (IR-Is) for DA in the nigrostriatal dopaminergic neuro ns by microphotometry. The DA-IR-Is in the substantia nigra pars compacta a nd neostriatum of young mice (2 months old) reached a minimal value 3 h aft er DAHP administration and returned to the control value 12 h after the adm inistration. However, in aged mice (10 months old), the minimal value was r eached 6 h after the administration and the value remained at approximate t o 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. (C) 1999 Elsevier Science Ireland Ltd. All rights reser ved.