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大鼠自愿饮用乙醇:生物胺及其潜在机制

Voluntary drinking of ethanol by the rat: biogenic amines and possible underlying mechanism.

作者信息

Messiha F S

出版信息

Pharmacol Biochem Behav. 1978 Sep;9(3):379-84. doi: 10.1016/0091-3057(78)90300-3.

Abstract

The present study evaluates the possible relationship between certain biogenic amine metabolites-produced changes in voluntary drinking of ethyl alcohol (ET) solution by the rat and their in vivo effects on the enzymes primarily involved in the hepatic metabolism of ET, i.e., liver alcohol-(L-ADH) and aldehyde dehydrogenase (L-ALDH). In experiments on voluntary intake of ET solution by the rat, compounds selected were injected, 0.5 mM/kg, IP. Administration of vanillylmandelic acid (VMA) and 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) markedly reduced ET drinking. Similar significant effects were seen after administration of the neutral metabolites of the biogenic amines tested, after injection of metanephrine or 3-methoxy-4-hydroxyphenylpyruvic acid. Threodihydroxyphenylserine but not L-dopa reduced ET intake by the rat. Treatment with peripheral decarboxylase inhibitors, i.e., carbidopa, 50 mg/kg, IP, significantly reduced ET drinking as contrasted with nonsignificant decline in ET consumption following benserazide, 500 mg/kg, IP. In the biochemical study, short-term administration of the compounds selected produced varied effects on L-ADH and L-ADH. It is suggested that alteration of hepatic ADH by the compounds tested might account for the observation reduced ET drinking thereby, indicating the contribution of peripheral sources rather than central factors in mediating the behavioral effects studied.

摘要

本研究评估了某些生物胺代谢产物与大鼠自愿饮用乙醇(ET)溶液变化之间的可能关系,以及它们对主要参与ET肝脏代谢的酶,即肝脏乙醇脱氢酶(L-ADH)和乙醛脱氢酶(L-ALDH)的体内作用。在大鼠自愿摄入ET溶液的实验中,以0.5 mM/kg的剂量腹腔注射所选化合物。注射香草扁桃酸(VMA)、5-羟吲哚乙酸(5HIAA)和高香草酸(HVA)后,ET饮用量显著减少。注射变肾上腺素或3-甲氧基-4-羟基苯丙酮酸后,所测试生物胺的中性代谢产物给药后也观察到类似的显著效果。L-多巴不能减少大鼠的ET摄入量,但L-苏氨酸二羟基苯丝氨酸可减少其摄入量。腹腔注射外周脱羧酶抑制剂,即50 mg/kg的卡比多巴,可显著减少ET饮用量,而腹腔注射500 mg/kg的苄丝肼后ET摄入量的下降不显著。在生化研究中,短期给予所选化合物对L-ADH和L-ADH产生了不同的影响。研究表明,所测试的化合物对肝脏ADH的改变可能是观察到的ET饮用量减少的原因,这表明在外周来源而非中枢因素在介导所研究的行为效应中发挥了作用。

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