Prevention of ethanol-induced behavioral stimulation by D-penicillamine: A sequestration agent for acetaldehyde
Prevention of ethanol-induced behavioral stimulation by D-penicillamine: A sequestration agent for acetaldehyde
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DOI：
10.1097/01.alc.0000171945.30494.af
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发表时间：
2005-07-01
影响因子：
3.2
通讯作者：
Aragon, CMG
中科院分区：
文献类型：
--
作者：
Font, L;Miquel, M;Aragon, CMG
背景：D-青霉胺是从青霉素中提取的一种巯基氨基酸，在体内对乙醇的第一代谢产物乙醛具有很高的选择性。大量研究支持这样一种观点，即大脑中乙醇代谢产生的乙醛在决定酒精摄入的一些行为影响方面发挥着关键作用。这项研究解决了两个问题。首先，我们测试了D-青霉胺是否能够改变乙醛对行为的抑制作用。方法：给小鼠注射D-青霉胺75.00 mg/kg，30min后分别给予0、100、200、300 mg/kg的乙醛灌胃。分别于注射生理盐水或1.2、1.8、2.4、3.0、3.6g/kg乙醇前30、90、150、210min分别给予D-青霉胺0.0、37.5、75、150、300 mg/kg。用可卡因(4 mg/kg)和咖啡因(15 mg/kg)两种药物研究D-青霉胺作用的特异性。结果：D-青霉胺可减轻乙醛(200和300 mg/kg)引起的行为抑制。此外，D-青霉胺还能有效地降低乙醇(1.8和2.4g/kg)诱导的小鼠的行为活动，而不改变自发活动。由于可卡因或咖啡因诱导的运动不受影响，这种巯基氨基酸可以特别地改变乙醇对运动的影响。结论：D-青霉胺是一种有效的乙醛封闭剂，可阻断乙醛和乙醇对动物的行为影响。这些结果表明，一些精神药理效应，经典地归因于乙醇，可能是由其第一代谢物乙醛介导的。
Background: D-Penicillamine, a sulfhydryl amino acid derived from penicillin, is a highly selective agent for sequestering in vivo acetaldehyde, the first metabolic product of ethanol. A substantial amount of research supports the idea that brain acetaldehyde, produced by central ethanol metabolism, plays a key role in determining some of the behavioral effects of ethanol administration. This study addressed two questions. First, we tested if D-penicillamine was able to modify the depressant effects of acetaldehyde on behavior. Second, we studied the effect Of D-penicillamine on ethanol-induced behavioral stimulation.Methods: Mice were pretreated with 75.00 mg/kg Of D-penicillamine, and 30 min later, they received acetaldehyde at 0, 100, 200, or 300 mg/kg intraperitoneally. Different groups of animals were treated with 0.0, 37.5, 75, 150, or 300 mg/kg Of D-penicillamine simultaneously 30, 90, 150, or 210 min before the intraperitoneal administration of saline or 1.2, 1.8, 2.4, 3.0, or 3.6 g/kg of ethanol, respectively. The specificity Of D-penicillamine effects was addressed using two drugs: cocaine (4 mg/kg) and caffeine (15 mg/kg).Results: Our results revealed that behavioral depression caused by acetaldehyde (200 and 300 mg/kg) could be attenuated by D-penicillamine treatment. In addition, D-penicillamine was also effective in lowering behavioral locomotion induced by ethanol (1.8 and 2.4 g/kg), without altering spontaneous locomotor activity. This sulfhydryl amino acid specifically modified the effect of ethanol on locomotion because cocaine- or caffeine-induced locomotion was unaffected. In addition, blood ethanol levels were not different between D-penicillamine- and saline-pretreated mice.Conclusions: Behavioral effects produced by acetalclehyde and ethanol are blocked when animals are treated with D-penicillamine, an effective sequestration agent for acetaldehyde. These results suggest that some of the psychopharmacological effects, classically attributed to ethanol, could be mediated by its first metabolite, acetaldehyde.