Miyazaki S, Imaizumi M, Machida H
Biology Laboratory, Research and Development Division, Yamasa Corporation, Chiba, Japan.
Pharmacol Biochem Behav. 1994 Nov;49(3):471-5. doi: 10.1016/0091-3057(94)90057-4.
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.
研究了新型中枢作用药物1-氨基-5-溴尿嘧啶（ABU）对大鼠脑单胺能神经递质水平的影响。在非应激条件下，ABU（腹腔注射20和30mg/kg）不影响单胺代谢，而地西泮（腹腔注射5mg/kg）可提高3-甲氧基-4-羟基苯乙二醇（MHPG）/去甲肾上腺素（NA）比值。1小时的固定应激可提高未用药大鼠不同脑区的MHPG/NA比值，但不提高高香草酸（HVA）加3,4-二羟基苯乙酸（DOPAC）/多巴胺（DA）比值或5-羟吲哚乙酸（5-HIAA）/血清素（5-HT）比值。ABU或地西泮预处理可抑制固定应激诱导的去甲肾上腺素能神经元激活。相比之下，电足部电击应激可提高MHPG/NA和HVA+DOPAC/DA比值。ABU或地西泮预处理可抑制电足部电击应激对去甲肾上腺素能和多巴胺能皮质神经元的激活。这些结果表明，这两种生理应激对单胺能神经元的影响不同，且其作用可被ABU和地西泮抑制。
