Smiałowska Maria, Wierońska Joanna M, Domin Helena, Zieba Barbara
Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Neuropsychopharmacology. 2007 Jun;32(6):1242-50. doi: 10.1038/sj.npp.1301258. Epub 2006 Nov 29.
Earlier studies conducted by our group and by other authors indicated that metabotropic glutamatergic receptor (mGluR) ligands might have anxiolytic activity and that amygdalar neuropeptide Y (NPY) neurons were engaged in that effect. Apart from the amygdala, the hippocampus, another limbic structure, also seems to be engaged in regulation of anxiety. It is rich in mGluRs and contains numerous NPY interneurons. In the present study, we investigated the anxiolytic activity of group II and III mGluR agonists after injection into the hippocampus, and attempted to establish whether hippocampal NPY neurons and receptors were engaged in the observed effects. Male Wistar rats were bilaterally microinjected with the group II mGluR agonist (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I), group III mGluR agonist O-Phospho-L-serine (L-SOP), NPY, the Y1 receptor antagonist BIBO 3304, and the Y2 receptor antagonist BIIE 0246 into the CA1 or dentate area (DG). The effect of those compounds on anxiety was tested in the elevated plus-maze. Moreover, the effects of L-CCG-I and L-SOP on the expression of NPYmRNA in the hippocampus were studied using in situ hybridization method. It was found that a significant anxiolytic effect was induced by L-SOP injection into the CA1 region or by L-CCG-I injection into the DG. The former effect was inhibited by BIBO 3304, the latter by BIIE 0246. NPY itself showed antianxiety action after injection into both structures. In the CA1 area, the effect of NPY was prevented by BIBO 3304, whereas in the DG by BIIE 0246. Both the mGluR agonists L-CCG-I and L-SOP induced a potent increase in NPYmRNA expression in the DG region of the hippocampal formation. The obtained results indicate that group II and III mGluR agonists, L-CCG-I and L-SOP, as well as NPY display anxiolytic activity in the hippocampus, but act differently in the CA1 and DG. It was observed that group III mGluRs and Y1 receptors were engaged in the response in the CA1 area, whereas group II mGluRs and Y2 receptors played a pivotal role in the DG region.
我们团队以及其他作者早期进行的研究表明，代谢型谷氨酸受体（mGluR）配体可能具有抗焦虑活性，并且杏仁核神经肽Y（NPY）神经元参与了这一效应。除了杏仁核，海马体作为另一个边缘系统结构，似乎也参与了焦虑的调节。海马体富含mGluR，并且含有大量NPY中间神经元。在本研究中，我们研究了向海马体注射II组和III组mGluR激动剂后的抗焦虑活性，并试图确定海马体中的NPY神经元和受体是否参与了所观察到的效应。将雄性Wistar大鼠双侧微量注射II组mGluR激动剂（2S,1'S,2'S）-2-（羧基环丙基）甘氨酸（L-CCG-I）、III组mGluR激动剂O-磷酸-L-丝氨酸（L-SOP）、NPY、Y1受体拮抗剂BIBO 3304以及Y2受体拮抗剂BIIE 0246至CA1区或齿状回（DG）。在高架十字迷宫中测试这些化合物对焦虑的影响。此外，使用原位杂交方法研究了L-CCG-I和L-SOP对海马体中NPYmRNA表达的影响。结果发现，向CA1区注射L-SOP或向DG区注射L-CCG-I均可诱导显著的抗焦虑作用。前者的作用被BIBO 3304抑制，后者被BIIE 0246抑制。NPY自身注射到这两个结构中均显示出抗焦虑作用。在CA1区，NPY的作用被BIBO 3304阻断，而在DG区被BIIE 0246阻断。mGluR激动剂L-CCG-I和L-SOP均能显著增加海马结构DG区的NPYmRNA表达。所得结果表明，II组和III组mGluR激动剂L-CCG-I和L-SOP以及NPY在海马体中均表现出抗焦虑活性，但在CA1区和DG区的作用方式不同。研究发现，III组mGluR和Y1受体参与了CA1区的反应，而II组mGluR和Y2受体在DG区起关键作用。
