NEUROHYPOPHYSEAL PEPTIDES AND ETHANOL TOLERANCE

精氨酸加压素(AVP)，一种哺乳动物抗利尿激素及其相关物质 当外源性给药时，多肽可以延长耐受时间 到乙醇。神经垂体肽对血管紧张素转换酶影响的相似性 支持容忍度和先前报道的对记忆整合的影响 假设，作为中枢神经系统适应的例子，这些现象可能 共享底层机制。“环境依赖型”的酒精耐受性 结果是对乙醇作用的条件性补偿反应， 并且有一个突出的“学习”部分。我们发现AVP坚持认为 环境依赖耐受性，与AVP对 学习和记忆。然而，AVP抑制了对 依赖环境的耐受性，可能是通过干扰动物的 对与酒精注射相关的线索的感知。首字母 对AVP拮抗剂的研究表明，内源性激素在 在维持宽容方面的作用。这些研究正在扩展到 研究V1和V2血管加压素特异性拮抗剂的作用 受体，为了表征调节激素的中枢神经系统受体 对耐受性的影响。内源性AVP的作用也是 通过研究AVP的生物合成(包括水平)进行研究 MRNA、前体分子和荷尔蒙本身)。 暴露会导致耐受性的发展。了解组织的作用 多肽激素在发育、表达和消散中的作用 对乙醇的耐受性形式可能会导致操作的良性手段 耐受性的发展，可能还有酒精摄入量的发展。

Arginine vasopressin (AVP), a mammalian antidiuretic hormone, and related peptides, when administered exogenously, prolong the duration of tolerance to ethanol. The similarities between neurohypophyseal peptide effects on tolerance and previously reported effects on memory consolidation supported the hypothesis that, as examples of CNS adaptation, these phenomena may share underlying mechanisms. "Environment-dependent" ethanol tolerance results from a conditioned compensatory response to the effects of ethanol, and has a prominent "learned" component. We found that AVP maintains environment-dependent tolerance, consistent with the effects of AVP on learning and memory. However, AVP inhibited the acquisition of environment-dependent tolerance, possibly by interfering with animals' perception of the cues associated with ethanol administration. Initial studies with antagonists of AVP suggested that the endogenous hormone plays a role in maintenance of tolerance. These studies are being extended to examine the effects of antagonists specific for V1 and V2 vasopressin receptors, in order to characterize the CNS receptors that mediate hormonal effects on tolerance. The role of endogenous AVP is also being investigated through studies of the biosynthesis of AVP (including levels of mRNA, precursor molecules, and hormone itself) during chronic ethanol exposure leading to tolerance development. Understanding the role of the peptide hormones in development, expression and dissipation of various forms of tolerance to ethanol may lead to benign means for the manipulation of the development of tolerance and, possibly, of ethanol intake.