Hoffman P L, Tabakoff B
Division of Intramural Clinical and Biological Research National Institute on Alcohol Abuse and Alcoholism Bethesda, Maryland 20892.
Alcohol Alcohol. 1989;24(3):251-2.
Functional tolerance to ethanol can be prolonged by administration of the neuropeptide arginine vasopressin (AVP), which acts at specific CNS receptors. AVP receptors in brain (lateral septum) have been shown to be localized, in part, presynaptically, and the mechanism of action of AVP may thus involve modulation of neurotransmitter release. AVP has also been found to increase the levels of mRNA for the cellular proto-oncogene, c-fos, in the septum and hippocampus. This response to AVP, which may be direct or indirect, may underlie the long-term neuroadaptive effects of the peptide. Studies with vasopressin antagonists have indicated a role for endogenous AVP in modulation of ethanol tolerance, and measurement of hypothalamic vasopressin mRNA by Northern blot analysis and in situ hybridization indicates that chronic ethanol ingestion may alter AVP synthesis. Tolerance to the aversive effects of ethanol has been postulated to influence alcohol drinking behavior in some individuals. Elucidation of the mechanism by which AVP affects ethanol tolerance may eventually lead to pharmacological means to modulate tolerance and, consequently, alcohol intake patterns.
通过给予神经肽精氨酸加压素（AVP）可延长对乙醇的功能性耐受，AVP作用于特定的中枢神经系统受体。已证明大脑（外侧隔区）中的AVP受体部分定位于突触前，因此AVP的作用机制可能涉及神经递质释放的调节。还发现AVP可增加隔区和海马中细胞原癌基因c-fos的mRNA水平。这种对AVP的反应可能是直接的或间接的，可能是该肽长期神经适应性作用的基础。使用加压素拮抗剂的研究表明内源性AVP在调节乙醇耐受中起作用，通过Northern印迹分析和原位杂交测量下丘脑加压素mRNA表明，长期摄入乙醇可能会改变AVP的合成。据推测，对乙醇厌恶作用的耐受会影响一些个体的饮酒行为。阐明AVP影响乙醇耐受的机制最终可能会导致调节耐受的药理学方法，从而改变酒精摄入模式。
