Behavioral Consequences of Hippocampal 5-HT7 Receptors Blockade in Stressed Rats.

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. © 2024 Wiley Periodicals LLC.

Citation

Adriana Colsera Pereira, Júlia Lopes Gonçalez, Thalita Aparecida Riul Prado, Rodrigo Campos-Cardoso, Giovana Vieira Viais Zagatto, Pedro Guilherme Pauletti Lorenzo, Cláudia Maria Padovan. Behavioral Consequences of Hippocampal 5-HT7 Receptors Blockade in Stressed Rats. Hippocampus. 2025 Jan;35(1):e23663

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PMID: 39644265

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