INTERACTIVE EFFECTS OF NEUROHYPOPHYSEAL NEUROPEPTIDES WITH RECEPTOR ANTAGONISTS ON PASSIVE-AVOIDANCE BEHAVIOR - MEDIATION BY A CEREBRAL NEUROHYPOPHYSEAL HORMONE RECEPTOR
INTERACTIVE EFFECTS OF NEUROHYPOPHYSEAL NEUROPEPTIDES WITH RECEPTOR ANTAGONISTS ON PASSIVE-AVOIDANCE BEHAVIOR - MEDIATION BY A CEREBRAL NEUROHYPOPHYSEAL HORMONE RECEPTOR
复制标题
DOI：
10.1073/pnas.88.4.1494
复制
发表时间：
1991-02-01
影响因子：
11.1
通讯作者：
KOVACS, G
中科院分区：
文献类型：
--
作者：
DEWIED, D;ELANDS, J;KOVACS, G
神经垂体神经肽(Arg8)-抗利尿激素（AVP）和[pGlu4，Cyt6]AVP-(4-8)（其中pGlu是热谷氨酸，Cyt是胱氨酸）在学习试验后立即给予脑室，促进大鼠一次性学习被动回避行为的保留。片段[pGlu4，Cyt6]AVP-(4-8)比AVP更有效。在学习试验后，将催产素（OXT）和[pGlu4，Cyt6]OXT-(4-8)注入脑室，也会产生相反的效果，并减弱被动回避行为。这个片段再次比母体分子更活跃。含有精氨酸的神经垂体激素催产素在“高”剂量（10 ng）下具有抗利尿激素样作用，在“低”剂量（0.1 ng）下具有oxt样作用。由于抗利尿激素能受体（V1）和催产素能受体在中枢神经系统中都已被证实，我们想知道V1、V2和OXT受体的特异性拮抗剂是否可以拮抗这些神经肽对被动回避行为的影响。这三种拮抗剂在阻断抗利尿素作用方面的活性大致相同，而片段[pGlu4]AVP-(4-8)和高剂量的抗利尿素更容易被OXT拮抗剂阻断。OXT拮抗剂可显著降低OXT、片段[pGlu4，Cyt6]OXT-(4-8)和低剂量催产素的减毒作用。这种效应也可以通过V1拮抗剂预处理而不是V2拮抗剂预处理来降低。这些结果表明，在大脑中存在一个独立的影响记忆过程的神经垂体激素受体复合物，它不同于外周的V1、V2和OXT受体。
The neurohypophyseal neuropeptides (Arg8)-vasopressin (AVP) and [pGlu4,Cyt6]AVP-(4-8) (where pGlu is pyroglutamic acid and Cyt is cystine) facilitate the retention of one-trial-learning passive avoidance behavior in rats when administered into the cerebral ventricle immediately after the learning trial. The fragment [pGlu4,Cyt6]AVP-(4-8) was considerably more effective than AVP. Oxytocin (OXT) and [pGlu4,Cyt6]OXT-(4-8) have the opposite effect and attenuate passive avoidance behavior also when administered into the cerebral ventricle after the learning trial. Again the fragment was more active than the parent molecule. The ancient arginine-containing neurohypophyseal hormone vasotocin in "high" doses (10 ng) had a vasopressin-like effect and in "low" doses (0.1 ng) had an OXT-like effect on passive avoidance behavior. Because both vasopressinergic (V1) and oxytocinergic receptors have been demonstrated in the central nervous system, we asked whether specific antagonists of the V1, V2, and OXT receptor could antagonize the effects of these neuropeptides on passive avoidance behavior. The three antagonists were approximately equally active in blocking the effect of vasopressin, whereas the fragment [pGlu4]AVP-(4-8) and the high dose of vasotocin were more readily blocked by the OXT antagonist. The attenuating effect of OXT, the fragment [pGlu4,Cyt6]OXT-(4-8), and the low dose of vasotocin was markedly reduced by the OXT antagonist. This effect could also be reduced by pretreatment with the V1 antagonist but not with the V2 antagonist. These results suggest the existence of a separate neurohypophyseal hormone receptor complex in the brain affecting memory processes that differs from the peripheral V1, V2, and OXT receptor.