海马内给药AP5的d-和l-异构体会破坏自发交替行为和诱发电位

David L. Walker , Paul E. Gold
{"title":"海马内给药AP5的d-和l-异构体会破坏自发交替行为和诱发电位","authors":"David L. Walker ,&nbsp;Paul E. Gold","doi":"10.1016/S0163-1047(05)80036-6","DOIUrl":null,"url":null,"abstract":"<div><p>We previously reported that systemically administered <em>N</em>-methyl-<span>d</span>-aspartate (NMDA) antagonists significantly impair spontaneous alternation behavior. Others have reported that the restricted blockade of hippocampal NMDA receptors disrupts performance on different tests of spatial learning and have suggested that the resulting impairments are attributable to a disruption of endogenous NMDA-dependent long-term potentiation (LTP). In the present study, we determined whether spontaneous alternation performance was disrupted by circumscribed blockade of hippocampal NMDA receptors as well as by a second class of compounds which disrupt LTP, protein kinase inhibitors. The effect of hippocampal NMDA blockade on inhibitory avoidance was also examined insofar as this behavior too is disrupted by systemically administered NMDA antagonists. When injected into the hippocampus 15 min prior to spontaneous alternation testing, the NMDA antagonists CPP and <span>d,l</span>-AP5 each decreased alternation rates. the specific protein kinase C (PKC) inhibitor, NPC 15437, also disrupted spontaneous alternation, whereas the more general kinase inhibitor, PMXB, did not. When injected 15 min prior to inhibitory avoidance training, CPP also impaired inhibitory avoidance learning as assessed during a subsequent test session, 48 h later. Interpretation of these data was complicated by the additional findings that intrahippocampal infusion of <span>l</span>-AP5 (which is inactive with respect to NMDA receptors) also disrupted alternation performance, and that both the <span>d</span>- and the <span>l</span>-isomers of AP5 as well as each kinase inhibitor dramatically disrupted evoked responses (i.e., population spike amplitude, spike latency, and EPSP slope), as recorded in the dentate gyrus and evoked by perforant path stimulation. These data indicate that behaviorally effective doses of AP5 may have effects which extend beyond NMDA blockade. Moreover, the effects of these compounds on hippocampal transmission, in general, suggest that attribution of the amnestic consequences of their administration to impaired LTP may be unwarranted.</p></div>","PeriodicalId":8732,"journal":{"name":"Behavioral and neural biology","volume":"62 2","pages":"Pages 151-162"},"PeriodicalIF":0.0000,"publicationDate":"1994-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0163-1047(05)80036-6","citationCount":"26","resultStr":"{\"title\":\"Intrahippocampal administration of both the d- and the l-isomers of AP5 disrupt spontaneous alternation behavior and evoked potentials\",\"authors\":\"David L. Walker ,&nbsp;Paul E. Gold\",\"doi\":\"10.1016/S0163-1047(05)80036-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>We previously reported that systemically administered <em>N</em>-methyl-<span>d</span>-aspartate (NMDA) antagonists significantly impair spontaneous alternation behavior. Others have reported that the restricted blockade of hippocampal NMDA receptors disrupts performance on different tests of spatial learning and have suggested that the resulting impairments are attributable to a disruption of endogenous NMDA-dependent long-term potentiation (LTP). In the present study, we determined whether spontaneous alternation performance was disrupted by circumscribed blockade of hippocampal NMDA receptors as well as by a second class of compounds which disrupt LTP, protein kinase inhibitors. The effect of hippocampal NMDA blockade on inhibitory avoidance was also examined insofar as this behavior too is disrupted by systemically administered NMDA antagonists. When injected into the hippocampus 15 min prior to spontaneous alternation testing, the NMDA antagonists CPP and <span>d,l</span>-AP5 each decreased alternation rates. the specific protein kinase C (PKC) inhibitor, NPC 15437, also disrupted spontaneous alternation, whereas the more general kinase inhibitor, PMXB, did not. When injected 15 min prior to inhibitory avoidance training, CPP also impaired inhibitory avoidance learning as assessed during a subsequent test session, 48 h later. Interpretation of these data was complicated by the additional findings that intrahippocampal infusion of <span>l</span>-AP5 (which is inactive with respect to NMDA receptors) also disrupted alternation performance, and that both the <span>d</span>- and the <span>l</span>-isomers of AP5 as well as each kinase inhibitor dramatically disrupted evoked responses (i.e., population spike amplitude, spike latency, and EPSP slope), as recorded in the dentate gyrus and evoked by perforant path stimulation. These data indicate that behaviorally effective doses of AP5 may have effects which extend beyond NMDA blockade. Moreover, the effects of these compounds on hippocampal transmission, in general, suggest that attribution of the amnestic consequences of their administration to impaired LTP may be unwarranted.</p></div>\",\"PeriodicalId\":8732,\"journal\":{\"name\":\"Behavioral and neural biology\",\"volume\":\"62 2\",\"pages\":\"Pages 151-162\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1994-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/S0163-1047(05)80036-6\",\"citationCount\":\"26\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Behavioral and neural biology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0163104705800366\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Behavioral and neural biology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0163104705800366","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 26

摘要

我们以前报道过,系统给药n -甲基-d-天冬氨酸(NMDA)拮抗剂显著损害自发交替行为。其他人报道,海马NMDA受体的限制性阻断会破坏不同空间学习测试的表现,并表明由此产生的损伤可归因于内源性NMDA依赖的长期增强(LTP)的破坏。在本研究中,我们确定自发交替性能是否被海马NMDA受体的限制性阻断以及第二类破坏LTP的化合物(蛋白激酶抑制剂)所破坏。海马NMDA阻断对抑制性回避的影响也被研究,因为这种行为也被系统给药的NMDA拮抗剂破坏。当在自发交替试验前15分钟注射到海马中时,NMDA拮抗剂CPP和d,l-AP5分别降低交替率。特异性蛋白激酶C (PKC)抑制剂NPC 15437也会破坏自发交替,而更一般的激酶抑制剂PMXB则不会。当在抑制回避训练前15分钟注射CPP时,在48小时后的后续测试中评估,CPP也会损害抑制回避学习。对这些数据的解释由于另外的发现而变得复杂:海马内输注l-AP5(对NMDA受体来说是无活性的)也会破坏交替表现,而且AP5的d-和l-异构体以及每种激酶抑制剂都会显著破坏诱发反应(即,在齿状回中记录的、通过穿孔路径刺激引起的群体峰振幅、峰潜伏期和EPSP斜率)。这些数据表明,行为有效剂量的AP5可能具有超越NMDA阻断的作用。此外,一般来说,这些化合物对海马传递的影响表明,将其给药的遗忘后果归因于LTP受损可能是没有根据的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Intrahippocampal administration of both the d- and the l-isomers of AP5 disrupt spontaneous alternation behavior and evoked potentials

We previously reported that systemically administered N-methyl-d-aspartate (NMDA) antagonists significantly impair spontaneous alternation behavior. Others have reported that the restricted blockade of hippocampal NMDA receptors disrupts performance on different tests of spatial learning and have suggested that the resulting impairments are attributable to a disruption of endogenous NMDA-dependent long-term potentiation (LTP). In the present study, we determined whether spontaneous alternation performance was disrupted by circumscribed blockade of hippocampal NMDA receptors as well as by a second class of compounds which disrupt LTP, protein kinase inhibitors. The effect of hippocampal NMDA blockade on inhibitory avoidance was also examined insofar as this behavior too is disrupted by systemically administered NMDA antagonists. When injected into the hippocampus 15 min prior to spontaneous alternation testing, the NMDA antagonists CPP and d,l-AP5 each decreased alternation rates. the specific protein kinase C (PKC) inhibitor, NPC 15437, also disrupted spontaneous alternation, whereas the more general kinase inhibitor, PMXB, did not. When injected 15 min prior to inhibitory avoidance training, CPP also impaired inhibitory avoidance learning as assessed during a subsequent test session, 48 h later. Interpretation of these data was complicated by the additional findings that intrahippocampal infusion of l-AP5 (which is inactive with respect to NMDA receptors) also disrupted alternation performance, and that both the d- and the l-isomers of AP5 as well as each kinase inhibitor dramatically disrupted evoked responses (i.e., population spike amplitude, spike latency, and EPSP slope), as recorded in the dentate gyrus and evoked by perforant path stimulation. These data indicate that behaviorally effective doses of AP5 may have effects which extend beyond NMDA blockade. Moreover, the effects of these compounds on hippocampal transmission, in general, suggest that attribution of the amnestic consequences of their administration to impaired LTP may be unwarranted.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信