NEUROHYPOPHYSEAL PEPTIDES AND ETHANOL TOLERANCE

精氨酸加压素（AVP）和相关肽，当给药时 外源性地，通过作用延长对乙醇的耐受时间 中枢神经系统V-1受体 以前的研究表明，刺激c- AVP在隔区的fos表达有助于这一作用， 多肽（AVP（4-9）、神经生长、神经生长和神经生长因子）的结构-活性研究进展 对乙醇耐受性的影响支持这一假设。 的 发现V-1受体拮抗剂增加了 乙醇耐受性表明内源性AVP对于 保持宽容。 研究用老鼠来控制糖尿病 尿崩症（DI）基因（不产生功能性加压素）， 来评估这个假设。 DI基因纯合子大鼠 获得了功能性乙醇耐受性，但比 正常大鼠或DI基因杂合的大鼠。 这些数据使我们 检查慢性乙醇处理期间AVP的合成。 在两种小鼠中 慢性乙醇可降低大鼠下丘脑AVP mRNA的表达 exposure. 这些数据，特别是在老鼠身上的数据，表明 乙醇是为了解偶联血管加压素的合成和分泌。 原位 杂交还显示，脱水增加，慢性 乙醇摄入减少，下丘脑区加压素mRNA 在SON和PVN外和终纹床核内， 下丘脑外核，其神经元投射到外侧 隔膜 这些结果表明加压素的增加 大脑中的合成是不必要的，以维持激素 宽容 了解AVP影响的机制 对乙醇的耐受性可能会导致良性的手段， 耐受性和酒精摄入量。

Arginine vasopressin (AVP) and related peptides, when administered exogenously, prolong the duration of tolerance to ethanol by an action at CNS V-1 receptors. Previous work suggested that stimulation of c- fos expression in the septum by AVP contributes to this action, and current structure-activity studies of peptide (AVP(4-9), nerve growth factor) effects on ethanol tolerance support this hypothesis. The finding that a V-1 receptor antagonist enhanced the rate of loss of ethanol tolerance suggested that endogenous AVP is important for maintaining tolerance. Studies with rats bred to contain the diabetes insipidus (DI) gene (which do not produce functional vasopressin) were carried out to evaluate this postulate. Rats homozygous for the DI gene acquired functional ethanol tolerance, but lost it more rapidly than normal rats or those heterozygous for the DI gene. These data led us to examine AVP synthesis during chronic ethanol treatment. In both mice and rats, hypothalamic AVP mRNA was decreased by chronic ethanol exposure. The data, particularly in rats, suggested that the effect of ethanol was to uncouple vasopressin synthesis and secretion. In situ hybridization also revealed that dehydration increased, and chronic ethanol ingestion decreased, vasopressin mRNA in hypothalamic areas outside the SON and PVN and in the bed nucleus of the stria terminalis, an extrahypothalamic nucleus whose neurons project to the lateral septum. These results indicate that an increase in vasopressin synthesis in brain is not necessary in order for the hormone to maintain tolerance. Understanding the mechanism by which AVP influences tolerance to ethanol may lead to benign means for the manipulation of tolerance and, possibly, of ethanol intake.