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向导水管周围灰质背侧微量注射甘丙肽会产生依赖范式的抗焦虑作用。

Galanin microinjection into the dorsal periaqueductal gray matter produces paradigm-dependent anxiolytic effects.

作者信息

Soares F R C, Silote G P, Almeida-Santos A F, Aguiar D C, Schenberg L C, Beijamini V

机构信息

Biochemistry and Pharmacology Postgraduate Program, Health Science Center, Federal University of Espirito Santo, Vitoria, ES 29043-900, Brazil.

Department of Pharmacology, Federal University of Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.

出版信息

Brain Res Bull. 2016 Mar;121:42-7. doi: 10.1016/j.brainresbull.2015.12.006. Epub 2016 Jan 2.

Abstract

Galanin is a peptide that is present in the central nervous system in mammals, including rodents and humans. The actions of galanin are mediated by three types of metabotropic receptors: GAL1, GAL2, and GAL3. GAL1 and GAL3 increase K(+) efflux, and GAL2 increases intracellular Ca(2+) levels. The distribution of galanin and its receptors suggests its involvement in fear and/or anxiety. The periaqueductal gray matter (PAG) is a key mediator of defensive behaviors that is both targeted by galaninergic projections and supplied with GAL1 receptors and, less markedly, GAL2 receptors. We examined the effects of galanin microinjections in the dorsal PAG (dPAG) on the performance of rats in different models of anxiety. Male Wistar rats (n=7-12) were implanted with guide cannulae in the dPAG. They received microinjections of either galanin (0.3, 1.0, and 3.0 nmol) or vehicle and were tested in the Vogel conflict test (VCT), elevated plus maze (EPM), and elevated T-maze (ETM). Rats that were tested in the ETM were further evaluated for exploratory activity in the open field test (OFT). Galanin microinjections had no effects on anxiety-like behavior in the EPM or VCT or exploratory activity in the EPM or OFT. In the ETM, however, microinjections of 3 nmol galanin impaired learned anxiety (i.e., avoidance of the open arms) without changing unconditioned fear (i.e., escape from the open arms). The present data suggest that galanin transmission in the dPAG inhibits the acquisition of anxiety-like responses in the ETM.

摘要

甘丙肽是一种存在于包括啮齿动物和人类在内的哺乳动物中枢神经系统中的肽。甘丙肽的作用由三种代谢型受体介导:GAL1、GAL2和GAL3。GAL1和GAL3增加钾离子外流,而GAL2增加细胞内钙离子水平。甘丙肽及其受体的分布表明其参与恐惧和/或焦虑。导水管周围灰质(PAG)是防御行为的关键调节因子,既接受甘丙肽能投射的靶向作用,又有GAL1受体,GAL2受体则较少。我们研究了向背侧导水管周围灰质(dPAG)微量注射甘丙肽对大鼠在不同焦虑模型中行为表现的影响。雄性Wistar大鼠(n = 7 - 12)在dPAG植入引导套管。它们接受了甘丙肽(0.3、1.0和3.0 nmol)或溶剂的微量注射,并在Vogel冲突试验(VCT)、高架十字迷宫(EPM)和高架T迷宫(ETM)中进行测试。在ETM中测试的大鼠在旷场试验(OFT)中进一步评估其探索活动。微量注射甘丙肽对EPM或VCT中的焦虑样行为或EPM或OFT中的探索活动没有影响。然而,在ETM中,注射3 nmol甘丙肽会损害习得性焦虑(即避开开放臂),而不改变无条件恐惧(即从开放臂逃脱)。目前的数据表明,dPAG中的甘丙肽传递会抑制ETM中焦虑样反应的习得。

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