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在大鼠进行沃格冲突测试时,抑制外侧导水管周围灰质中的 NMDA 受体/一氧化氮通路可产生类似抗焦虑的效果。

Inhibition of the NMDA receptor/Nitric Oxide pathway in the dorsolateral periaqueductal gray causes anxiolytic-like effects in rats submitted to the Vogel conflict test.

机构信息

Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Av Bandeirantes 3900, Ribeirão Preto, SP, 14049900, Brazil.

出版信息

Behav Brain Funct. 2009 Sep 23;5:40. doi: 10.1186/1744-9081-5-40.

Abstract

BACKGROUND

Several studies had demonstrated the involvement of the dorsolateral portion of periaqueductal grey matter (dlPAG) in defensive responses. This region contains a significant number of neurons containing the enzyme nitric oxide synthase (NOS) and previous studies showed that non-selective NOS inhibition or glutamate NMDA-receptor antagonism in the dlPAG caused anxiolytic-like effects in the elevated plus maze.

METHODS

In the present study we verified if the NMDA/NO pathway in the dlPAG would also involve in the behavioral suppression observed in rats submitted to the Vogel conflict test. In addition, the involvement of this pathway was investigated by using a selective nNOS inhibitor, Nomega-propyl-L-arginine (N-Propyl, 0.08 nmol/200 nL), a NO scavenger, carboxy-PTIO (c-PTIO, 2 nmol/200 nL) and a specific NMDA receptor antagonist, LY235959 (4 nmol/200 nL).

RESULTS

Intra-dlPAG microinjection of these drugs increased the number of punished licks without changing the number of unpunished licks or nociceptive threshold, as measure by the tail flick test.

CONCLUSION

The results indicate that activation of NMDA receptors and increased production of NO in the dlPAG are involved in the anxiety behavior displayed by rats in the VCT.

摘要

背景

几项研究表明,中脑导水管周围灰质的背外侧部分(dlPAG)参与了防御反应。该区域包含大量含有酶一氧化氮合酶(NOS)的神经元,先前的研究表明,dlPAG 中非选择性 NOS 抑制或谷氨酸 NMDA 受体拮抗作用会导致高架十字迷宫中的焦虑样效应。

方法

在本研究中,我们验证了 dlPAG 中的 NMDA/NO 通路是否也参与了在接受 Vogel 冲突测试的大鼠中观察到的行为抑制。此外,通过使用选择性 nNOS 抑制剂 Nomega-propyl-L-arginine(N-Propyl,0.08 nmol/200 nL)、NO 清除剂 carboxy-PTIO(c-PTIO,2 nmol/200 nL)和特定的 NMDA 受体拮抗剂 LY235959(4 nmol/200 nL),研究了该途径的参与情况。

结果

这些药物的 dlPAG 内微注射增加了受惩罚舔的次数,而不改变不受惩罚舔的次数或痛觉阈值,如尾巴拍打测试所测量的。

结论

结果表明,dlPAG 中 NMDA 受体的激活和 NO 生成的增加参与了大鼠在 VCT 中表现出的焦虑行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e30/2762983/c2a7dfec75a3/1744-9081-5-40-1.jpg

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