Wu P H, Liu J F, Mihic S J, Kalant H
Department of Pharmacology, Faculty of Medicine, University of Toronto, Ontario, Canada.
Pharmacol Biochem Behav. 1992 Feb;41(2):409-14. doi: 10.1016/0091-3057(92)90119-z.
AVP maintains ethanol (EtOH) tolerance after cessation of chronic EtOH treatment. However, the acute interaction of AVP and EtOH has not been well characterized. Rats were trained on a moving belt and the EtOH dose-response relationship (range 1.0-2.0 g/kg) was determined after pretreatment with saline, AVP (2.5-40 micrograms SC or 10 ng ICV), the AVP-V1 receptor antagonist [Des-Gly9,d(CH2)5(1),O-Et-Tyr2, Val4,Arg8]-vasopressin (10 ng ICV), or AVP in combination with the V1 antagonist. AVP produced a 16% decrease in the EtOH ED50 when given either SC or ICV; this decrease, which appears to represent true potentiation rather than additivity, was prevented by the preadministration of the V1 antagonist. Other rats were made EtOH-tolerant by 7 daily injections of either EtOH alone (1.8 g/kg IP) or EtOH (1.5 g/kg IP) + AVP (10 micrograms SC), followed by a practice session on the moving belt. In both sets of tolerant animals, AVP potentiation of acute EtOH effects was still seen on day 6. The mechanism of AVP potentiation of EtOH-induced impairment is unknown, but the failure of the V1 antagonist alone to alter the effect of EtOH suggests that endogenous AVP is not involved directly in modulating EtOH intoxication.
在慢性乙醇治疗停止后，抗利尿激素（AVP）维持乙醇（EtOH）耐受性。然而，AVP与EtOH的急性相互作用尚未得到充分表征。将大鼠置于移动带上进行训练，并在给予生理盐水、AVP（2.5 - 40微克皮下注射或10纳克脑室内注射）、AVP-V1受体拮抗剂[去甘氨酸9，d(CH2)5(1)，O-乙基酪氨酸2，缬氨酸4，精氨酸8]-加压素（10纳克脑室内注射）或AVP与V1拮抗剂联合预处理后，确定EtOH剂量 - 反应关系（范围为1.0 - 2.0克/千克）。当皮下或脑室内给予AVP时，EtOH的半数有效剂量（ED50）降低了16%；这种降低似乎代表真正的增强而非相加作用，预先给予V1拮抗剂可阻止这种降低。其他大鼠通过每日7次单独注射EtOH（1.8克/千克腹腔注射）或EtOH（1.5克/千克腹腔注射）+ AVP（10微克皮下注射）使其产生EtOH耐受性，随后在移动带上进行练习。在两组耐受性动物中，在第6天仍可见AVP对急性EtOH效应的增强作用。AVP增强EtOH诱导损伤的机制尚不清楚，但单独使用V1拮抗剂未能改变EtOH的效应，这表明内源性AVP不直接参与调节EtOH中毒。
