Jackson H C, Ramsay E, Nutt D J
Reckitt & Colman Psychopharmacology Unit, Department of Pharmacology, School of Medical Sciences, University Walk, Bristol, U.K.
Alcohol Alcohol. 1992 Jul;27(4):373-9.
This study shows inhibition of the increase in locomotor activity induced by ethanol (2 g/kg i.p.) in mice by a low dose (0.1 mg/kg i.p.) of the non-opioid beta-endorphin fragment ORG 5878 (des-enkephalin-gamma-endorphin). ORG 5878 (0.1 mg/kg i.p.) also significantly antagonised the large increase in electroshock seizure threshold produced by ethanol (1.5 g/kg i.p.). In contrast, the hypothermia induced by ethanol (2 g/kg i.p.) was not altered by ORG 5878 (0.1 mg/kg i.p.). The effects of ORG 5878 showed an abnormal dose-response relationship, in that a high dose (1 mg/kg i.p.) did not significantly suppress any of the behavioural effects of ethanol examined although there was some indication that it attenuated the stimulant action of ethanol. ORG 5878 (0.1, 1 mg/kg i.p.) did not have any intrinsic effects on locomotion, seizure threshold or body temperature in mice. These results are the first demonstration that ORG 5878 may act as an ethanol antagonist in some paradigms.
本研究表明，低剂量（腹腔注射0.1毫克/千克）的非阿片类β-内啡肽片段ORG 5878（去甲脑啡肽-γ-内啡肽）可抑制乙醇（腹腔注射2克/千克）诱导的小鼠运动活性增加。ORG 5878（腹腔注射0.1毫克/千克）还显著拮抗了乙醇（腹腔注射1.5克/千克）引起的电击惊厥阈值大幅升高。相比之下，ORG 5878（腹腔注射0.1毫克/千克）并未改变乙醇（腹腔注射2克/千克）诱导的体温过低。ORG 5878的作用呈现出异常的剂量反应关系，即高剂量（腹腔注射1毫克/千克）虽然有迹象表明其减弱了乙醇的兴奋作用，但并未显著抑制所检测的乙醇的任何行为效应。ORG 5878（腹腔注射0.1、1毫克/千克）对小鼠的运动、惊厥阈值或体温没有任何内在影响。这些结果首次证明ORG 5878在某些实验范式中可能作为乙醇拮抗剂发挥作用。
