Effect of 1-amino-5-bromouracil on brain monoamine metabolism in rats

The effect of 1-amino-5-bromouracil (ABU), a novel central-acting agent, on monoaminergic neurotransmitter levels of rat brain was investigated. Under the nonstressed condition, ABU (20 and 30 mg/kg intraperitoneally [IP]) did not affect monoamine metabolism, whereas diazepam (5 mg/kg IP) increased the 3-methoxy-4-hydroxyphenylethylene glycol (MHPG)/noradrenaline (NA) ratio. One-hour immobilization stress increased the MHPG/NA ratio in various brain regions of drug-naive rats, but did not increase the homovanilic acid (HVA) plus 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) ratio or the 5-hydroxyindole acetic acid (5-HIAA)/serotonin (5-HT) ratio. Pretreatment with ABU or diazepam suppressed the activation of noradrenergic neurons induced by immobilization stress. By contrast, electric foot shock stress increased the MHPG/NA and HVA+DOPAC/DA ratios. Pretreatment with ABU or diazepam suppressed the activation of noradrenergic and dopaminergic cortical neurons by electric foot shock stress. These results indicate that these two physiologic stresses affected monoaminergic neurons differently and that their effects were suppressed by ABU and diazepam.