Funck V R, Fracalossi M P, Vidigal A P P, Beijamini V
Biochemistry and Pharmacology Graduate Program, Federal University of Espirito Santo, Brazil.
Department of Pharmaceutical Sciences, Health Science Centre, Federal University of Espirito Santo, Brazil.
Brain Res. 2018 May 15;1687:74-81. doi: 10.1016/j.brainres.2018.02.036. Epub 2018 Feb 27.
Galanin, a peptide expressed in mammalian brain regions, has been implicated in anxiety and depression. Galanin signalling occurs through three G protein-linked receptors (GAL, GAL and GAL). Galanin regulates the release of neurotransmitters in some brain regions related to anxiety, including the hippocampus. GAL is the most abundant galanin receptor in the dorsal hippocampus. In this study, we evaluated whether galanin administered in the dorsal hippocampus affected anxiety-like behaviours of rats. We also investigated if GAL receptors are involved in the anxiogenic-like effect of galanin using a GAL antagonist, M871. To achieve these objectives, male adult Wistar rats received intra-dorsal hippocampal delivery of galanin (0.3 and 1.0 nmol/0.5 µl) or vehicle in experiment 1 and GAL antagonist M871 (1.0 and 3.0 nmol/0.5 µl) or vehicle in experiment 2. Twenty min after administration of drugs, the animals were tested in the elevated plus-maze (EPM). Galanin (1.0 nmol) induced anxiogenic-like behaviours, while the GAL receptor antagonist M871 (3.0 nmol) induced anxiolytic-like behaviours in rats exposed to the EPM, indicating a tonic effect of galanin. In experiment 3, we evaluated whether previous infusion of the GAL antagonist M871 (1 or 2 nmol) in the dorsal hippocampus would block the anxiogenic-like effect of galanin in rats tested in the EPM. We showed that M871 (2.0 nmol) counteracted the anxiogenic-like effect of galanin infused in the dorsal hippocampus of rats. Altogether, our results provide evidence that galanin promotes pharmacological and tonic anxiogenic-like effects in the dorsal hippocampus, possibly mediated by GAL receptors.
甘丙肽是一种在哺乳动物脑区表达的肽，与焦虑和抑郁有关。甘丙肽信号传导通过三种G蛋白偶联受体（GAL1、GAL2和GAL3）发生。甘丙肽在包括海马体在内的一些与焦虑相关的脑区调节神经递质的释放。GAL1是背侧海马体中最丰富的甘丙肽受体。在本研究中，我们评估了在背侧海马体中给予甘丙肽是否会影响大鼠的焦虑样行为。我们还使用甘丙肽拮抗剂M871研究了GAL受体是否参与甘丙肽的致焦虑样效应。为实现这些目标，在实验1中，成年雄性Wistar大鼠接受背侧海马体注射甘丙肽（0.3和1.0 nmol/0.5 μl）或溶剂；在实验2中，接受甘丙肽拮抗剂M871（1.0和3.0 nmol/0.5 μl）或溶剂。给药20分钟后，动物在高架十字迷宫（EPM）中进行测试。甘丙肽（1.0 nmol）在暴露于EPM的大鼠中诱发了焦虑样行为，而GAL受体拮抗剂M871（3.0 nmol）诱发了抗焦虑样行为，表明甘丙肽具有紧张性效应。在实验3中，我们评估了先前在背侧海马体中注射甘丙肽拮抗剂M871（1或2 nmol）是否会阻断在EPM中测试的大鼠中甘丙肽的致焦虑样效应。我们发现M871（2.0 nmol）抵消了注入大鼠背侧海马体中甘丙肽的致焦虑样效应。总之，我们的结果提供了证据，表明甘丙肽在背侧海马体中促进药理学和紧张性致焦虑样效应，可能由GAL受体介导。
