File S E, Gonzalez L E, Andrews N
Psychopharmacology Research Unit, United Medical and Dental Schools of Guy's and St. Thomas's Hospitals Division of Pharmacology, London, United Kingdom.
J Neurosci. 1996 Aug 1;16(15):4810-5. doi: 10.1523/JNEUROSCI.16-15-04810.1996.
The purpose of this study was to determine the roles of the presynaptic 5-hydroxtryptamine1A (5-HT1A) receptors in the median raphé nucleus (MRN) and of the postsynaptic 5-HT1A receptors in its projection area of the dorsal hippocampus in the social interaction and elevated plus-maze tests of anxiety. Direct administration of the 5-HT1A receptor agonist (+/-)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT, 200 ng) into the MRN had significant anxiolytic effects in all three test situations examined (social interaction, plus-maze trails 1 and 2). These anxiolytic effects were antagonized by a silent dose (200 ng) of the 5-HT1A receptor antagonist WAY 100635, confirming that they were mediated by 5-HT1A receptors. In contrast, after bilateral administration to the dorsal hippocampus, 8-0H-DPAT (100 ng) had significant anxiogenic effects in the social interaction test and in plus-maze trial 2. These anxiogenic effects were antagonized by silent doses of 5-HT1A receptor antagonists [(+)WAY 100135, 10 mg/kg s.c., and intrahippocampal (+/-)tertatolol, 3 microg, respectively], confirming mediation by 5-HT1A receptors. In rats naive to the plus-maze, neither 8-OH-DPAT (50, 100, or 200 ng) nor the 5-HT1A receptor antagonist (+/-)tertatolol (3 microgram) had any significant effect when administered to the dorsal hippocampus. This demonstrates that previous experience of a rat in the plus-maze has a major effect on the sensitivity of dorsal hippocampal 5-HT1A receptors, as we have demonstrated previously for the 5-HT1A receptors in the dorsal raphé nucleus. Overall, our results provide evidence that stimulation of the presynaptic 5-HT1A receptors in the MRN results in an anxiolytic action, whereas stimulation of the post-synaptic 5-HT1A receptors in its projection area results in an anxiogenic effect. These results are consistent with an overall reduction in 5-HT neurotransmission in the dorsal hippocampus having an anxiolytic effect, and they explain the relatively weak anxiolytic profile detected when 5-HT1A receptor agonists are given systemically.
本研究旨在确定中缝正中核（MRN）中突触前5-羟色胺1A（5-HT1A）受体以及背侧海马投射区域中突触后5-HT1A受体在社交互动和高架十字迷宫焦虑测试中的作用。向MRN直接注射5-HT1A受体激动剂（±）-8-羟基二丙基氨基四氢萘（8-OH-DPAT，200 ng）在所有三种测试情境（社交互动、十字迷宫试验1和2）中均产生显著的抗焦虑作用。这些抗焦虑作用被5-HT1A受体拮抗剂WAY 100635的无活性剂量（200 ng）所拮抗，证实它们是由5-HT1A受体介导的。相反，向背侧海马双侧注射8-OH-DPAT（100 ng）后，在社交互动测试和十字迷宫试验2中产生显著的致焦虑作用。这些致焦虑作用被5-HT1A受体拮抗剂的无活性剂量[（+）WAY 100135，10 mg/kg皮下注射以及海马内注射（±）替他洛尔，3 μg]所拮抗，证实是由5-HT1A受体介导的。在初次接触十字迷宫的大鼠中，向背侧海马注射8-OH-DPAT（50、100或200 ng）或5-HT1A受体拮抗剂（±）替他洛尔（3 μg）均无任何显著作用。这表明大鼠之前在十字迷宫中的经历对背侧海马5-HT1A受体的敏感性有重大影响，正如我们之前对背侧中缝核中5-HT1A受体所证明的那样。总体而言，我们的结果提供了证据，表明刺激MRN中的突触前5-HT1A受体导致抗焦虑作用，而刺激其投射区域中的突触后5-HT1A受体则导致致焦虑作用。这些结果与背侧海马中总体5-羟色胺神经传递减少具有抗焦虑作用一致，并且解释了全身给予5-HT1A受体激动剂时检测到的相对较弱的抗焦虑特征。
