NEUROHYPOPHYSEAL PEPTIDES AND ETHANOL TOLERANCE

精氨酸加压素(AVP)及相关多肽的应用 外源性，延长对乙醇的耐受时间。vbl.使用 与之选择性相互作用的多肽激动剂和拮抗剂 加压素V1和V2受体。我们将其描述为V1 脑内介导加压素能力的受体 保持酒精耐受性。我们还确定了加压素的特征 脑内结合部位的定量放射自显影。这个 结合位点数最高的是外侧隔， 在背侧海马区、下丘脑区和 丘脑区域。具有V1和V2选择性的置换研究 激动剂和拮抗剂表明，细胞内的结合部位 外侧隔具有V1受体的特征。6-0HDA 治疗显著减少了AVP结合位点的数量。 5，7-二羟色胺(5，7-DHT)治疗不能。以前的工作 表明完整的大脑去甲肾上腺素系统是 维持酒精耐量的AVP：因此，AVP可能作用于V1 去甲肾上腺素能神经元终末受体改变 神经递质的释放，从而影响耐受性。另一个 可能的(突触后)作用机制包括刺激 原癌基因c-fos的表达 被认为与学习或记忆有关。AVP 侧脑室注射后，侧隔c-fos表达增加。 这可能代表了AVP的直接或间接作用。我们的工作 内源性精氨酸加压素在维持血管紧张素转换酶活性中起作用。 乙醇耐受性，导致我们研究AVP在 慢性乙醇治疗。乙醇对小鼠和大鼠的影响 不同方法对下丘脑AVP mRNA表达均有下调作用。然而。 血浆中AVP水平因乙醇方法的不同而不同 治疗，表明其他因素，如脱水或 压力可能会影响这些水平。了解角色和 精氨酸加压素在发育、表达和转录中的作用机制 消除对乙醇的耐受性可能会导致 操纵耐受性，可能还有酒精摄入量。

Arginine vasopressin (AVP) and related peptides, when administered exogenously, prolong the duration of tolerance to ethanol. Using peptide agonists and antagonists that interact selectively with vasopressin V1 and V2 receptors. we characterized as V1 the receptors in brain that mediate the ability of vasopressin to maintain ethanol tolerance. We have also characterized vasopressin binding sites in brain by quantitative autoradiography. The highest concentration of binding sites was in the lateral septum, with lower densities in dorsal hippocampus, hypothalamus and thalamic areas. Displacement studies with V1- and V2-selective agonists and antagonists indicated that binding sites in the lateral septum have characteristics of V1 receptors. 6-0HDA treatment significantly reduced the number of AVP binding sites in lateral septum, while 5,7-DHT treatment did not. Previous work showed that intact brain noradrenergic systems are necessary for AVP to maintain ethanol tolerance: thus, AVP may act at V1 receptors on terminals of noradrenergic neurons to alter neurotransmitter release and thus influence tolerance. Another possible (postsynaptic) mechanism of action involves stimulation of expression of the proto-oncogene c-fos, which has previously been postulated to be involved in learning or memory. AVP increases c-fos expression in lateral septum after icv injection. This may represent a direct or indirect action of AVP. Our work also showed that endogenous AVP plays a role in maintenance of ethanol tolerance, leading us to investigate AVP synthesis during chronic ethanol treatment. In mice and rats exposed to ethanol by different methods, hypothalamic AVP mRNA was decreased. However. AVP levels in plasma varied, depending on the method of ethanol treatment, suggesting that other factors such as dehydration or stress may influence these levels. Understanding the role and mechanism of action of AVP in development, expression and dissipation of tolerance to ethanol may lead to benign means for the manipulation of tolerance and, possibly, of ethanol intake.