{"title":"Behavioral Consequences of Hippocampal 5-HT7 Receptors Blockade in Stressed Rats","authors":"Adriana Colsera Pereira, Júlia Lopes Gonçalez, Thalita Aparecida Riul Prado, Rodrigo Campos-Cardoso, Giovana Vieira Viais Zagatto, Pedro Guilherme Pauletti Lorenzo, Cláudia Maria Padovan","doi":"10.1002/hipo.23663","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Serotonin (5-HT) has long been involved in response to stress and its effect may be, in part, mediated by 5-HT1a and 5-HT7 receptor subtypes in different brain structures. Both pre- and post-synaptic activation of 5-HT1a receptor, respectively, in the rat median raphe nucleus (MnRN) and hippocampus, lead to adaptation to acute inescapable stressors such as restraint and forced swim. 5-HT7 receptor (5HT7r), a stimulatory G-protein coupled receptor, has also been investigated as a possible candidate for mediating stress response. In the MnRN, activation of 5-HT7r has antidepressant effects, while in the hippocampus, 5HT7r mRNA expression is increased after exposure to restraint stress, but the functional significance of these receptors remains to be determined. Therefore, the aim of this study was to investigate whether blockade of hippocampal 5HT7r would prevent and/or attenuate the behavioral effects of stress. Male adult Wistar rats with bilateral cannulas aimed at the dorsal hippocampus were restrained for 2 h and tested in the elevated plus maze (EPM) 24 h later. SB 258741 (3 nmoles/0.5 μL/side; selective 5HT7r antagonist) was administered bilateraly into the hippocampus according to the experimental protocol: immediately before or after stress, or 24 h after it (immediately before the test). In a second experiment, rats were exposed to 15 min. of forced swim, and tested 24 h later. Intra-hippocampal treatment was performed as described for the restraint stress protocol. We found that blockade of hippocampal 5-HT7r immediately after, but not before, the exposure to restraint or forced swim attenuated stress-induced behavioral changes. Similar results were obtained when SB was administered before the test in previously stressed rats. Our data suggest that activation of hippocampal 5-HT7r is crucial for the consolidation and retrieval of aversive stimulus-related memories, such as those caused by a stressful experience, probably through mechanisms involving stress-induced changes in 5-HT7r expression.</p>\n </div>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"35 1","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hippocampus","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hipo.23663","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Serotonin (5-HT) has long been involved in response to stress and its effect may be, in part, mediated by 5-HT1a and 5-HT7 receptor subtypes in different brain structures. Both pre- and post-synaptic activation of 5-HT1a receptor, respectively, in the rat median raphe nucleus (MnRN) and hippocampus, lead to adaptation to acute inescapable stressors such as restraint and forced swim. 5-HT7 receptor (5HT7r), a stimulatory G-protein coupled receptor, has also been investigated as a possible candidate for mediating stress response. In the MnRN, activation of 5-HT7r has antidepressant effects, while in the hippocampus, 5HT7r mRNA expression is increased after exposure to restraint stress, but the functional significance of these receptors remains to be determined. Therefore, the aim of this study was to investigate whether blockade of hippocampal 5HT7r would prevent and/or attenuate the behavioral effects of stress. Male adult Wistar rats with bilateral cannulas aimed at the dorsal hippocampus were restrained for 2 h and tested in the elevated plus maze (EPM) 24 h later. SB 258741 (3 nmoles/0.5 μL/side; selective 5HT7r antagonist) was administered bilateraly into the hippocampus according to the experimental protocol: immediately before or after stress, or 24 h after it (immediately before the test). In a second experiment, rats were exposed to 15 min. of forced swim, and tested 24 h later. Intra-hippocampal treatment was performed as described for the restraint stress protocol. We found that blockade of hippocampal 5-HT7r immediately after, but not before, the exposure to restraint or forced swim attenuated stress-induced behavioral changes. Similar results were obtained when SB was administered before the test in previously stressed rats. Our data suggest that activation of hippocampal 5-HT7r is crucial for the consolidation and retrieval of aversive stimulus-related memories, such as those caused by a stressful experience, probably through mechanisms involving stress-induced changes in 5-HT7r expression.
期刊介绍:
Hippocampus provides a forum for the exchange of current information between investigators interested in the neurobiology of the hippocampal formation and related structures. While the relationships of submitted papers to the hippocampal formation will be evaluated liberally, the substance of appropriate papers should deal with the hippocampal formation per se or with the interaction between the hippocampal formation and other brain regions. The scope of Hippocampus is wide: single and multidisciplinary experimental studies from all fields of basic science, theoretical papers, papers dealing with hippocampal preparations as models for understanding the central nervous system, and clinical studies will be considered for publication. The Editor especially encourages the submission of papers that contribute to a functional understanding of the hippocampal formation.